T cell epitope selection: dominance may be determined by both affinity for major histocompatibility complex and stoichiometry of epitope.
The majority of T cell hybridomas produced in the BALB/c mouse in response to immunization with lambda repressor cI recognize a peptide fragment comprising of residues 12 to 26 (P12-26). Some other parts of the cI (P1-14, P33-48 and P73-88) are defective in generating T cell responses in the BALB/c mouse. P73-88 may be converted into a T cell determinant if a few more amino acid residues are included (P67-88). Together with P46-67 and P80-102, most peptides derived from cI were capable of eliciting T cell responses by themselves in BALB/c mouse. The mechanisms underlying the selection of P12-26 over the other epitopes when lambda repressor was used as immunogen were examined. The dominant response to P12-26 was attenuated by tolerizing with intravenous administration of P12-26. Under such treatment the T cell response to P12-26 was reduced by 80% but there was no enhancement on the responses toward other epitopes. The selection of P12-26 is, thus, unlikely to be due to a competition at the T cell level. It was also found that the dominance of P12-26 was not simply due to a higher affinity of P12-26 for major histocompatibility complex molecules. For example P12-26 binds better to I-Ad molecule than P80-102, but co-injection with equimole of P12-26 only slightly inhibited P80-102-induced T cell response. Instead, it required a few molar excess of P12-26 to effectively block the association of P80-102 with I-Ad molecules and to inhibit the T cell immunity to P80-102. Since epitopes such as P46-67, P67-88 and P80-102 were generated from lambda repressor cI at a lower molar basis than that of P12-26, it is suggested that the dominance of P12-26 was probably generated by such stoichiometry difference, in addition to the higher affinity of P12-26 for I-Ad molecules.
Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan, R.O.C.
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Lai
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001667:Binding, Competitive; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007108:Immune Tolerance; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D012097:Repressor Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins
D004268:DNA-Binding Proteins; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D010455:Peptides; D012097:Repressor Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins