Selective contact during TCR recognition.
Recent structural analysis of the peptide-MHC complex reveals that an antigenic peptide binds to MHC in only one conformation and that side chains anchoring in the binding pocket would not contact TCR. The identification of all the MHC-anchoring residues on an antigenic peptide is a prerequisite to understand how a given peptide interacts with the TCR. In a combination of binding analysis and model simulation, model peptide lambda repressor cl 16-26 was shown to bind to I-Ek through four anchor residues (Leu18, IIe21, Glu23 and Lys26), a pattern found in many I-Ek-binding peptides. TCR reactivity analysis clearly indicates a great variation in the interaction with cl 16-26 by T cells generated from different strains of I-Ek-bearing mice. Most of the T cell generated from A/J mice reacted with the central regions of cl 16-26, while there is a great diversity on the recognition of cl 16-26 by T cells from C3H and B10.BR mice. Despite the diverse interactions with antigenic peptide by these T cells, most TCR-E-k contacts are limited to the central region of the I-Ek beta-chain. T cells recognizing only the N-terminal part of cl 16-26 were found to contact I-Ek at nearly the same residues as T cells interacting with the C-terminal of cl 16-26. TCR-I-Ek recognition was apparently independent of TCR-cl 16-26 contact. The discordant TCR-peptide and TCR-MHC interaction may represent a unique feature of TCR recognition.
Feng
M H
MH
Graduate Institute of Microbiology and Immunology, National Yang-Ming Medical School, Taipei, Taiwan, ROC.
Shen
Y C
YC
Chou
D L
DL
Lai
M Z
MZ
Liaw
Y C
YC
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D001665:Binding Sites; D016466:CHO Cells; D006224:Cricetinae; D015798:HLA-DR1 Antigen / Q000737:chemistry; D000949:Histocompatibility Antigens Class II / Q000737:chemistry*; D051379:Mice; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D018448:Models, Immunological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology
D015798:HLA-DR1 Antigen; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D017260:Receptor-CD3 Complex, Antigen, T-Cell