Role of peptide backbone in T cell recognition.
T cells recognize self and nonself peptides presented by molecules of the MHC. Amino acid substitutions in the antigenic peptide showed that T cell specificity is highly degenerate. Recently, determination of the crystal structure of several TCR/MHC-peptide complexes suggested that the peptide backbone may significantly contribute to the interaction with the TCR. To directly investigate the role of the peptide backbone in T cell recognition, we performed a methylene-amino scan on the backbone of an antigenic peptide and measured the capacity of such pseudopeptides to bind their cognate MHC molecule, to sensitize target cells for T cell lysis, and to stimulate IL-2 secretion by two T cell hybridomas. For one of these pseudopeptides, we prepared fluorescent tetramers of MHC molecules and compared the staining of two T cell hybridomas. Our results demonstrate that the peptide backbone has an important contribution to TCR binding and suggest that some interactions between the peptide backbone and the TCR may be partially conserved. We discuss this finding in the perspective of TCR plasticity and T cell function.
Calbo
S
S
Unité de Biologie Moléculaire du Gène, Institut National de la Santé et de la Recherche Médicale Unit 277, Institut Pasteur, Paris, France.
Guichard
G
G
Bousso
P
P
Muller
S
S
Kourilsky
P
P
Briand
J P
JP
Abastado
J P
JP
D000818:Animals; D002999:Clone Cells; D006183:H-2 Antigens / Q000378:metabolism; D015236:HLA-C Antigens / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D006825:Hybridomas; D051379:Mice; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011487:Protein Conformation; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
D006183:H-2 Antigens; C024755:H-2K(K) antigen; D015236:HLA-C Antigens; C038653:HLA-C*03 antigen; D009842:Oligopeptides