Changes at peptide residues buried in the major histocompatibility complex (MHC) class I binding cleft influence T cell recognition: a possible role for indirect conformational alterations in the MHC class I or bound peptide in determining T cell recognition.
Recent crystallographic studies on two peptide complexes with the mouse Kb molecule have shown that peptide binding appears to alter the conformation of the class I alpha-helical regions that flank the antigen binding cleft. Given that this study also showed that much of the foreign peptide is buried within the class I binding cleft with only a small portion accessible for direct interaction with the components of the T cell receptor, this finding suggests that at least some component of T cell specificity may arise as a consequence of peptide-induced conformational changes in the class I structure. To assess this possibility, we have made systematic substitutions at residues within the Kb-restricted determinant from ovalbumin (OVA257-264) that are thought to be buried on binding to the class I molecule. We have found that changes in this determinant at the completely buried second residue (P2) can influence T cell recognition without affecting binding to Kb, suggesting that the substitutions may indirectly determine T cell recognition by altering the conformation of the class I molecule or the bound peptide.
Chen
W
W
Department of Clinical Immunology, Flinders Medical Centre, Bedford Park, South Australia.
McCluskey
J
J
Rodda
S
S
Carbone
F R
FR
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D015395:Histocompatibility Antigens Class I / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D006825:Hybridomas / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008285:Major Histocompatibility Complex; D051379:Mice; D010047:Ovalbumin / Q000032:analysis; D011485:Protein Binding; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D014407:Tumor Cells, Cultured
D000596:Amino Acids; D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin