Positive selection of transgenic receptor-bearing thymocytes by K^b antigen is altered by K^b mutations that involve peptide binding

A specific interaction between the class I major histocompatibility complex molecule K^b and thymocytes expressing the antigen receptor from the cytolytic T lymphocyte 2C enhances maturation of T cells of the CD8 lineage in transgenic mice. By analyzing transgenic mice backcrossed to K^bm mutant strains of mice, we have identified five bm mutations of the K^b antigen-encoding gene that alter the positive selection of thymocytes induced by K^b antigen. Compared with K^b, K^bm10 and K^bm1 did not induce significant maturation of 2C T-cell receptor-bearing thymocytes, and K^bm8 antigen positively selected for transgenic thymocytes only weakly. Altering residue 77 of K^b molecule from aspartic acid to serine made K^bm3 and K^bm11 allogeneic targets for the 2C antigen receptor and caused deletion of transgenic thymocytes. This deletion spared T cells that expressed low levels of CD8, a result differing from the total deletion of CD8-bearing T cells seen in mice that expressed the original target alloantigen L^d. This evidence indicates that (i) self-peptides bound to thymic major histocompatibility complex molecules can influence the positive selection of thymocytes and (ii) thymocytes with apparently weak interaction with self-major histocompatibility complex antigens can escape clonal deletion.