Limited plasticity in T cell recognition of modified T cell receptor contact residues in MHC class II bound peptides.
The balance between specific and degenerate T cell recognition of MHC class II bound peptides is crucial for T cell repertoire selection, and holds important implications for protective immunity versus autoimmunity. To investigate the degree of degeneracy in T cell recognition, we applied selected modifications to T cell receptor (TCR) contact residue amino acids in the MHC class II bound epitope gpMBP72-85. By using glycosylated amino acids, as an example of a posttranslational modification, large alterations were applied. Small modifications were accomplished by exchanging an arginine residue for a citrulline or an ornithine residue. Finally, the unmodified TCR contact residue side chains were shifted one atom position to the left, using peptoid residues. Both these large and subtle changes in the wild type (WT) peptide caused lack of recognition by WT peptide specific monoclonal and polyclonal T cells. Furthermore, T cells specific for the modified peptides did not cross recognize the WT peptide. Using a set of additional compounds, we investigated the specificity of these T cell populations into detail. Our data reveal a strongly limited plasticity in T cell recognition, and a high specificity for TCR contact residue side chains.
de Haan
Ellen C
EC
Department of Medicinal Chemistry, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, PO Box 80082, 3508 TB Utrecht, The Netherlands.
Wagenaar-Hilbers
Josée P A
JP
Liskamp
Rob M J
RM
Moret
Ed E
EE
Wauben
Marca H M
MH
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002241:Carbohydrates / Q000737:chemistry; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D006031:Glycosylation; D006168:Guinea Pigs; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000378:metabolism*; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D015394:Molecular Structure; D004676:Myelin Basic Protein / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D034444:Peptoids / Q000276:immunology; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000596:Amino Acids; D000911:Antibodies, Monoclonal; D002241:Carbohydrates; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D034444:Peptoids; D011948:Receptors, Antigen, T-Cell; C118872:myelin basic protein 72-85