T cell receptor interactions with class I heavy-chain influence T cell selection.
The interaction of the T cell receptor (TCR) with peptide in the binding site of the major histocompatibility complex molecule provides the basis for T cell recognition during immune surveillance, repertoire development, and tolerance. Little is known about the extent to which repertoire selection is influenced directly by variation of the structure of the class I heavy chain. We find that the 2C TCR, normally positively selected in the context of the K(b) molecule, is minimally selected into the CD8 lineage in the absence of antigen-processing genes. This finding underscores the importance of peptides in determining the positive-selecting class I ligands in the thymus. In contrast, K(bm3), a variant class I molecule that normally exerts a negative selection pressure on 2C-bearing T cells, positively selects 2C transgenic T cells into the CD8 lineage in an antigen-processing gene-deficient environment. These findings indicate that structural changes in the heavy chain can have direct influence in T cell recognition, from which we conclude that the nature of TCR interaction with class I heavy chain influences the array of TCRs selected during development of the functional adult repertoire.
Kuhns
S T
ST
Departments of Biochemistry and Molecular Biology, Mayo Clinic/Foundation, Rochester, MN 55905, USA.
Tallquist
M D
MD
Johnson
A J
AJ
Mendez-Fernandez
Y
Y
Pease
L R
LR
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D017951:Antigen Presentation; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002460:Cell Line; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D018528:ATP-Binding Cassette Transporters; D006183:H-2 Antigens; D011948:Receptors, Antigen, T-Cell