Positive Selection of Transgenic Receptor-Bearing Thymocytes by KbAntigen is Altered by KbMutations that Involve Peptide Binding

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 87; no. 16; pp. 6186 - 6190
• Main Authors: Sha, William C., Nelson, Christopher A., Newberry, Rodney D., Pullen, Jeffrey K., Pease, Larry R., Russell, John H., Loh, Dennis Y.
• Format: Journal Article
• Language: English
• Published: National Academy of Sciences of the United States of America 01-08-1990
• Subjects: Antigens; Mice; Molecules; Positive selection; Spleen cells; T cell antigen receptors; T lymphocytes; Thymocytes; Transgenic animals; Transponders
• ISSN: 0027-8424; 1091-6490

A specific intraction between the class I major histocompatibility complex molecule Kband 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 Kbmmutant strains of mice, we have identified five bm mutations of the Kbantigen-encoding gene that alter the positive selection of thymocytes induced by Kbantigen. Compared with Kb, Kbm10and Kbm1did not induce significant maturation of 2C T-cell receptor-bearing thymocytes, and Kbm8antigen positively selected for transgenic thymocytes only weakly. Altering residue 77 of Kbmolecule from aspartic acid to serine made Kbm3and Kbm11allogeneic 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 Ld. 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.