T cell recognition of the immunodominant Sendai virus NP324-332/Kb epitope is focused on the center of the peptide.
The CTL response to Sendai virus in C57BL/6 mice is directed almost exclusively to a single H-2Kb-restricted epitope derived from the virus nucleoprotein, NP324-332 (FAPGNYPAL). We have previously shown that the repertoire of T cells elicited by this epitope following primary Sendai virus infection is very diverse. The current experiments were undertaken to determine how a diverse array of TCR are able to interact with a single class I epitope. Crystallographic analysis of NP324-332 bound to Kb has shown that the side chains of peptide residues F1, G4, N5, and A8 protrude toward the solvent and are potentially available for recognition by the TCR. Notably, the N5 residue protrudes prominently from the peptide-binding site due to its localization on a bulge in the center of NP324-332. To determine the importance of these residues for T cell recognition, we analyzed the response of a large panel of hybridomas to NP324-332 analogues substituted at these four positions. The data suggested that there is dominant recognition of the central G4 and N5 residues at the center of the peptide. However, individual hybridomas exhibited distinct patterns of fine specificity for residues F1 and A8, in that they were dependent on one, both, or neither of these residues for recognition of NP324-332. These data are consistent with a critical role for the G4 and N5 residues in governing NP324-332/Kb recognition by T cells and may have implications for T cell recognition of class-I restricted epitopes in general.
Cole
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GA
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Hogg
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TL
Woodland
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DL
D000595:Amino Acid Sequence; D000818:Animals; D003461:Crystallography; D018604:Epitope Mapping; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006825:Hybridomas; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010222:Parainfluenza Virus 1, Human / Q000276:immunology*; D018184:Paramyxoviridae Infections / Q000276:immunology*; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; D010455:Peptides; D014764:Viral Proteins