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Antigen recognition depends on detection of antigen by special receptors. Antigen recognition depends on cellular cooperation. Cellular cooperation is controlled by recognition of MHC-encoded receptors.¡t8 A * 7ª  ó Ÿ¨.Clonal Selection Theory (F. Macfarlane Burnet)¡/ª / Ÿ¨×pre-existence of of many different potential antibody producing cells each cell displays surface receptors for specific antigens antigen encounter selects cells What prevents recognition/destruction of self tissues?¡bØ# 5 >ª Ø ó Ÿ¨-Postulates of the Clonal Selection Hypothesisª . Ÿ¨3Each lymphocyte bears a single type of receptor of a unique specificity Interaction between a foreign molecule and a lymphocyte receptor capable of binding that molecule with high affinity leads to lymphocyte activation The differentiated effector cells derived from an activated lymphocyte will bear receptors of identical specificity to those of the parental cell from which that lymphocyte was derived Lymphocytes bearing receptors specific for self molecules are deleted at an early stage in lymphocyte development and are therefore absent from the repertoire¡’45C„Zª 4 ó Ÿ¨)Diversity of Lymphocyte Antigen Receptorsª * Ÿ¨”Variable region of antigen receptor encoded by sets of gene segments During lymphocyte development somatic gene rearrangement create unique combinations of gene segments Once recombinant events have occurred, further rearrangement is prohibited Receptor specificity of a lymphocyte cannot change Each lymphocyte bears many copies of the unique receptor At least 108 different lymphocytes in an individual¡Ú•( R & !(ª • ó Ÿ¨7Genomic Organization of heavy- and light-chain segmentsª 8 Ÿª ó Ÿ¨&Development of the Antibody Repertoireª ' Ÿ¨øThe antibody repertoire is generated during B cell development by DNA rearrangements that combine and assemble variable-region gene segments (somatic diversification theory) Diversity is enhanced by hypermutation in mature B cells (germline theory)¡HùŽ<ª@Ç       óŸ¨ESome Comments on Cluster of Differentiation/Designation (CD) Antigens¡FF(ª F Ÿ¨¥What are they? Differentiation antigens Expressed by cells at distinct stages of differentiation Expressed by cells having different functions How are they detected?¡6€€ª ¦ óŸ¨*Fluorescence-Activated Cell Sorting (FACS)¡++$ª + Ÿª ó Ÿ¨Lymphocyte Populationsª  Ÿ¨NB lymphocytes Plasma cells T lymphocytes Helper/Inducer (CD4) Suppressor (CD8)¡&)&)&ª O ó Ÿ¨T Cell Recognition of Antigenª  Ÿ¨sRecognize antigen peptide fragments bound to specialize cell surface molecules on antigen-presenting cells (APC). Molecules are encoded by major histocompatibility complex Peptides are displayed to T cells as peptide:MHC complexes T cell antigen receptors recognize peptide:MHC complexes Each MHC molecule can bind numerous different peptides Two classes of MHC molecules¡Œt® 2 ª&‘  Ñ ó Ÿ¨4Major Histocompatibility Complex (MHC) Gene Products¡55(ª&   Ÿ¨>Class I Antigen is usually endogenous (e.g. viral proteins). CD8+ Cytotoxic T Lymphocytes (CTLs) recognize antigen in association with class I MHC gene product on APC. Class II Molecules Antigen is usually extracellular. CD4+ Helper T Lymphocytes recognize antigen in association with class II MHC gene product on APC.¡¤ „ g ^ª&[  à ó Ÿ¨,Cellular Cooperation and Antigen Recognitionª - Ÿª ó Ÿ¨B Cell Antigen Recognitionª  Ÿ¨ïCell surface immunoglobulin receptor or B-cell receptor (IgM and IgD) Antigen contact initiates B-cell activation, clonal expansion, maturation to plasma cell Antigen receptor is identical to immunoglobulin that will ultimately be produced¡\ð )^ 4ª@A  /  w óŸ¨Cellular Cooperationª  Ÿª óŸ¨,Clonal Expansion Following Antigen Exposure ¡--$ª - Ÿª óŸ¨The Bottom Lineª  Ÿ ºIn order to initiate an immune response antigen must be recognized. Antigen recognition depends on detection of antigen by special receptors. Antigen recognition depends on cellular cooperation. Cellular cooperation is controlled by recognition of MHC-encoded receptors. 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žçxÚãè�….úñøÛ80Ä W4M}ˆ¢?ºèÃÎøáè2œ;˜Õß·~?¬`ÿ{Žbð$¯-ÇTžè·W…#¬ÿCª{Žrð$xQ€Fþoâé×âõJl/îIÿi¾8rð$ï�Àm>€_ï›ìàz6;+Üÿi'9rð$ ®hèË>ùÈÁ"ºf[gÒÿi �92ð$8"ŸÙzÍÜâGÆS~švéÿ­#ù9Bð$&~¿”ª´ Ø¨3óáÚŒÿZâºRð$Øì.ŠKµb™°|µžÿâMm# ðl€�ƒ†A¿ÀÁÄÅAËœ1ÍÎÐÑ×ÿ?0ñ QÜ¿ßÿ@ñ÷ð8ó€ó€Ðçÿ úgþý4UdUd�³X4ÐHÎ;ˆÿÿÿýÿÿ³ pûppû¨ º“°öÊš;­”ÇÊš;<ý4ddddà³Xº“°öÊš;­”ÇÊš;ö¸<ý4!d!dà³Xº“°öÊš;­”ÇÊš;ö¸ˆ¨Š0º___PPT10‹ ÀÀŠhº___PPT2001‹Dˆ<‰4X€à?Ù Ú%ðÆóŸ¨Lecture 4 Antigen Recognition¡(ª Ÿª óŸ¨Overviewª Ÿ¨In order to initiate an immune response antigen must be recognized. Antigen recognition depends on detection of antigen by special receptors. Antigen recognition depends on cellular cooperation. Cellular cooperation is controlled by recognition of MHC-encoded receptors.¡t8 A * 7ª ó Ÿ¨.Clonal Selection Theory (F. Macfarlane Burnet)¡/ª /Ÿ¨×pre-existence of of many different potential antibody producing cells each cell displays surface receptors for specific antigens antigen encounter selects cells What prevents recognition/destruction of self tissues?¡bØ# 5 >ª Øó Ÿ¨-Postulates of the Clonal Selection Hypothesisª .Ÿ¨3Each lymphocyte bears a single type of receptor of a unique specificity Interaction between a foreign molecule and a lymphocyte receptor capable of binding that molecule with high affinity leads to lymphocyte activation The differentiated effector cells derived from an activated lymphocyte will bear receptors of identical specificity to those of the parental cell from which that lymphocyte was derived Lymphocytes bearing receptors specific for self molecules are deleted at an early stage in lymphocyte development and are therefore absent from the repertoire¡’45C„Zª 4ó Ÿ¨)Diversity of Lymphocyte Antigen Receptorsª *Ÿ¨”Variable region of antigen receptor encoded by sets of gene segments During lymphocyte development somatic gene rearrangement create unique combinations of gene segments Once recombinant events have occurred, further rearrangement is prohibited Receptor specificity of a lymphocyte cannot change Each lymphocyte bears many copies of the unique receptor At least 108 different lymphocytes in an individual¡Ú•( R & !(ª •ó Ÿ¨7Genomic Organization of heavy- and light-chain segmentsª 8Ÿª ó Ÿ¨&Development of the Antibody Repertoireª 'Ÿ¨øThe antibody repertoire is generated during B cell development by DNA rearrangements that combine and assemble variable-region gene segments (somatic diversification theory) Diversity is enhanced by hypermutation in mature B cells (germline theory)¡HùŽ<ª2Ç  óŸ¨ESome Comments on Cluster of Differentiation/Designation (CD) Antigens¡FF(ª FŸ¨¥What are they? Differentiation antigens Expressed by cells at distinct stages of differentiation Expressed by cells having different functions How are they detected?¡6€€ª ¦óŸ¨*Fluorescence-Activated Cell Sorting (FACS)¡++$ª +Ÿª ó Ÿ¨Lymphocyte Populationsª Ÿ¨NB lymphocytes Plasma cells T lymphocytes Helper/Inducer (CD4) Suppressor (CD8)¡&)&)&ª Oó Ÿ¨T Cell Recognition of Antigenª Ÿ¨sRecognize antigen peptide fragments bound to specialize cell surface molecules on antigen-presenting cells (APC). Molecules are encoded by major histocompatibility complex Peptides are displayed to T cells as peptide:MHC complexes T cell antigen receptors recognize peptide:MHC complexes Each MHC molecule can bind numerous different peptides Two classes of MHC molecules¡Œt® 2 ª‘Ñó Ÿ¨4Major Histocompatibility Complex (MHC) Gene Products¡55(ªŸ¨>Class I Antigen is usually endogenous (e.g. viral proteins). CD8+ Cytotoxic T Lymphocytes (CTLs) recognize antigen in association with class I MHC gene product on APC. Class II Molecules Antigen is usually extracellular. CD4+ Helper T Lymphocytes recognize antigen in association with class II MHC gene product on APC.¡¤ „ g ^ª[àó Ÿ¨,Cellular Cooperation and Antigen Recognitionª -Ÿª ó Ÿ¨B Cell Antigen Recognitionª Ÿ¨ïCell surface immunoglobulin receptor or B-cell receptor (IgM and IgD) Antigen contact initiates B-cell activation, clonal expansion, maturation to plasma cell Antigen receptor is identical to immunoglobulin that will ultimately be produced¡\ð )^ 4ª2A/wóŸ¨Cellular Cooperationª Ÿª óŸ¨,Clonal Expansion Following Antigen Exposure ¡--$ª -Ÿª óŸ¨The Bottom Lineª Ÿ ºIn order to initiate an immune response antigen must be recognized. Antigen recognition depends on detection of antigen by special receptors. Antigen recognition depends on cellular cooperation. Cellular cooperation is controlled by recognition of MHC-encoded receptors. 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0Ò€ÕÈ·DTimesGarde:¨É:H:HX`·Xp³Ë¼IðîXp³ÿ·DTahomaarde:¨É:H:HX`·Xp³Ë¼IðîXp³ÿ" ·DArialarde:¨É:H:HX`·Xp³Ë¼IðîXp³ÿ"0·DWingdingse:¨É:H:HX`·Xp³Ë¼IðîXp³ÿ@·DHelveticae:¨É:H:HX`·Xp³Ë¼IðîXp³ÿ"P·DAvant Garde:¨É:H:HX`·Xp³Ë¼IðîXp³ÿ¤€cÿÿÿÿ¥0.ÿ«ÿ@  @@``€€©  @£nÿý?" dd@ÿÿïÿÿÿÿÿÿ  @@``€€ ðððt1y     BwQ]�ð`bð$T–˜�NÒ‹¤ßòЇÏ{`ÿ{Žbð$¯-ÇTžè·W…#¬ÿCª{Žrð$xQ€Fþoâé×âõJl/îIÿi¾8rð$ï�Àm>€_ï›ìàz6;+Üÿi'9rð$ ®hèË>ùÈÁ"ºf[gÒÿi �9Bð$8"ŸÙzÍÜâGÆS~švéÿ­#<ÊBð$&~¿”ª´ Ø¨3óáÚŒÿZâºRð$Øì.ŠKµb™°|µžÿâMm# ðl€�ƒ†A¿ÀÁÄÅAËœ1ÍÎÐÑ×ÿ?0ñ QÜ¿ßÿ@ñ÷ð8ó€ó€Ð+ÿ úgþý4UdUd�³X4ШÉ: ÿÿÿHýÿÿ³ pûppû¨ º“°öÊš;­”ÇÊš;<ý4ddddà³Xº“°öÊš;­”ÇÊš;ö¸<ý4!d!dà³Xº“°öÊš;­”ÇÊš;ö¸<ý4BdBdà³Xº“°öÊš;­”ÇÊš;Ðö¸ˆ¨Š0º___PPT10‹ ÀÀŠhº___PPT2001‹Dˆ<‰4X€à?Ù Ú%ð´óŸ¨Lecture 4 Antigen Recognition¡(ª Ÿª óŸ¨Overviewª Ÿ¨In order to initiate an immune response antigen must be recognized. Antigen recognition depends on detection of antigen by special receptors. Antigen recognition depends on cellular cooperation. Cellular cooperation is controlled by recognition of MHC-encoded receptors.¡t8 A * 7ª ó Ÿ¨.Clonal Selection Theory (F. Macfarlane Burnet)¡/ª /Ÿ¨×pre-existence of of many different potential antibody producing cells each cell displays surface receptors for specific antigens antigen encounter selects cells What prevents recognition/destruction of self tissues?¡bØ# 5 >ª Øó Ÿ¨-Postulates of the Clonal Selection Hypothesisª .Ÿ¨3Each lymphocyte bears a single type of receptor of a unique specificity Interaction between a foreign molecule and a lymphocyte receptor capable of binding that molecule with high affinity leads to lymphocyte activation The differentiated effector cells derived from an activated lymphocyte will bear receptors of identical specificity to those of the parental cell from which that lymphocyte was derived Lymphocytes bearing receptors specific for self molecules are deleted at an early stage in lymphocyte development and are therefore absent from the repertoire¡’45C„Zª 4ó Ÿ¨)Diversity of Lymphocyte Antigen Receptorsª *Ÿ¨”Variable region of antigen receptor encoded by sets of gene segments During lymphocyte development somatic gene rearrangement create unique combinations of gene segments Once recombinant events have occurred, further rearrangement is prohibited Receptor specificity of a lymphocyte cannot change Each lymphocyte bears many copies of the unique receptor At least 108 different lymphocytes in an individual¡Ú•( R & !(ª •ó Ÿ¨7Genomic Organization of heavy- and light-chain segmentsª 8Ÿª ó Ÿ¨&Development of the Antibody Repertoireª 'Ÿ¨øThe antibody repertoire is generated during B cell development by DNA rearrangements that combine and assemble variable-region gene segments (somatic diversification theory) Diversity is enhanced by hypermutation in mature B cells (germline theory)¡HùŽ<ª2Ç  óŸ¨ESome Comments on Cluster of Differentiation/Designation (CD) Antigens¡FF(ª FŸ¨¥What are they? Differentiation antigens Expressed by cells at distinct stages of differentiation Expressed by cells having different functions How are they detected?¡6€€ª ¦óŸ¨*Fluorescence-Activated Cell Sorting (FACS)¡++$ª +Ÿª ó Ÿ¨Lymphocyte Populationsª Ÿ¨NB lymphocytes Plasma cells T lymphocytes Helper/Inducer (CD4) Suppressor (CD8)¡&)&)&ª Oó Ÿ¨T Cell Recognition of Antigenª Ÿ¨sRecognize antigen peptide fragments bound to specialize cell surface molecules on antigen-presenting cells (APC). Molecules are encoded by major histocompatibility complex Peptides are displayed to T cells as peptide:MHC complexes T cell antigen receptors recognize peptide:MHC complexes Each MHC molecule can bind numerous different peptides Two classes of MHC molecules¡Œt® 2 ª‘Ñó Ÿ¨4Major Histocompatibility Complex (MHC) Gene Products¡55(ªŸ¨>Class I Antigen is usually endogenous (e.g. viral proteins). CD8+ Cytotoxic T Lymphocytes (CTLs) recognize antigen in association with class I MHC gene product on APC. Class II Molecules Antigen is usually extracellular. CD4+ Helper T Lymphocytes recognize antigen in association with class II MHC gene product on APC.¡¤ „ g ^ª[àó Ÿ¨,Cellular Cooperation and Antigen Recognitionª -Ÿª ó Ÿ¨B Cell Antigen Recognitionª Ÿ¨ïCell surface immunoglobulin receptor or B-cell receptor (IgM and IgD) Antigen contact initiates B-cell activation, clonal expansion, maturation to plasma cell Antigen receptor is identical to immunoglobulin that will ultimately be produced¡\ð )^ 4ª2A/wóŸ¨Cellular CooperationŸª óŸ¨,Clonal Expansion Following Antigen Exposure ¡--$ª -Ÿª óŸ¨The Bottom Lineª Ÿ ºIn order to initiate an immune response antigen must be recognized. Antigen recognition depends on detection of antigen by special receptors. Antigen recognition depends on cellular cooperation. Cellular cooperation is controlled by recognition of MHC-encoded receptors. 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Antigen recognition depends on detection of antigen by special receptors. Antigen recognition depends on cellular cooperation. Cellular cooperation is controlled by recognition of MHC-encoded receptors.¡t8 A * 7ª ó Ÿ¨.Clonal Selection Theory (F. Macfarlane Burnet)¡/ª /Ÿ¨×pre-existence of of many different potential antibody producing cells each cell displays surface receptors for specific antigens antigen encounter selects cells What prevents recognition/destruction of self tissues?¡bØ# 5 >ª Øó Ÿ¨-Postulates of the Clonal Selection Hypothesisª .Ÿ¨3Each lymphocyte bears a single type of receptor of a unique specificity Interaction between a foreign molecule and a lymphocyte receptor capable of binding that molecule with high affinity leads to lymphocyte activation The differentiated effector cells derived from an activated lymphocyte will bear receptors of identical specificity to those of the parental cell from which that lymphocyte was derived Lymphocytes bearing receptors specific for self molecules are deleted at an early stage in lymphocyte development and are therefore absent from the repertoire¡’45C„Zª 4ó Ÿ¨)Diversity of Lymphocyte Antigen Receptorsª *Ÿ¨”Variable region of antigen receptor encoded by sets of gene segments During lymphocyte development somatic gene rearrangement create unique combinations of gene segments Once recombinant events have occurred, further rearrangement is prohibited Receptor specificity of a lymphocyte cannot change Each lymphocyte bears many copies of the unique receptor At least 108 different lymphocytes in an individual¡Ú•( R & !(ª •ó Ÿ¨7Genomic Organization of heavy- and light-chain segmentsª 8Ÿª ó Ÿ¨&Development of the Antibody Repertoireª 'Ÿ¨øThe antibody repertoire is generated during B cell development by DNA rearrangements that combine and assemble variable-region gene segments (somatic diversification theory) Diversity is enhanced by hypermutation in mature B cells (germline theory)¡HùŽ<ª2Ç  óŸ¨ESome Comments on Cluster of Differentiation/Designation (CD) Antigens¡FF(ª FŸ¨¥What are they? Differentiation antigens Expressed by cells at distinct stages of differentiation Expressed by cells having different functions How are they detected?¡6€€ª ¦óŸ¨*Fluorescence-Activated Cell Sorting (FACS)¡++$ª +Ÿª ó Ÿ¨Lymphocyte Populationsª Ÿ¨NB lymphocytes Plasma cells T lymphocytes Helper/Inducer (CD4) Suppressor (CD8)¡&)&)&ª Oó Ÿ¨T Cell Recognition of Antigenª Ÿ¨sRecognize antigen peptide fragments bound to specialize cell surface molecules on antigen-presenting cells (APC). Molecules are encoded by major histocompatibility complex Peptides are displayed to T cells as peptide:MHC complexes T cell antigen receptors recognize peptide:MHC complexes Each MHC molecule can bind numerous different peptides Two classes of MHC molecules¡Œt® 2 ª‘Ñó Ÿ¨4Major Histocompatibility Complex (MHC) Gene Products¡55(ªŸ¨>Class I Antigen is usually endogenous (e.g. viral proteins). CD8+ Cytotoxic T Lymphocytes (CTLs) recognize antigen in association with class I MHC gene product on APC. Class II Molecules Antigen is usually extracellular. CD4+ Helper T Lymphocytes recognize antigen in association with class II MHC gene product on APC.¡¤ „ g ^ª[àó Ÿ¨,Cellular Cooperation and Antigen Recognitionª -Ÿª ó Ÿ¨B Cell Antigen Recognitionª Ÿ¨ïCell surface immunoglobulin receptor or B-cell receptor (IgM and IgD) Antigen contact initiates B-cell activation, clonal expansion, maturation to plasma cell Antigen receptor is identical to immunoglobulin that will ultimately be produced¡\ð )^ 4ª2A/wóŸ¨Cellular CooperationŸª óŸ¨,Clonal Expansion Following Antigen Exposure ¡--$ª -Ÿª óŸ¨The Bottom Lineª Ÿ ºIn order to initiate an immune response antigen must be recognized. Antigen recognition depends on detection of antigen by special receptors. Antigen recognition depends on cellular cooperation. Cellular cooperation is controlled by recognition of MHC-encoded receptors. 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