Role of TCR‐restricting MHC density and thymic environment on selection and survival of cells expressing low‐affinity T cell receptors

• Published in: European journal of immunology Vol. 34; no. 4; pp. 1041 - 1049
• Main Authors: Martinic, Marianne M., Rocha, Benedita, McCoy, Kathy D., Hengartner, Hans, Zinkernagel, Rolf M.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 01.04.2004
• Subjects: Animals; Female; H-2 Antigens - immunology; H-Y Antigen - immunology; Histocompatibility Antigen H-2D; H‐Y TCR; Male; MHC density; Mice; Mice, Transgenic; Receptors, Antigen, T-Cell - immunology; Self Tolerance; T cell selection and survival; Thymic and athymic environment; Thymus Gland - cytology; Thymus Gland - immunology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.200424920

H‐Y‐specific T cell receptor (TCR) transgenic mice express an MHC class I H‐2Db‐restricted TCR specific for a male antigen‐derived peptide (H‐Y). Selection and survival of cells expressing this low‐affinity TCR were analyzed under optimal and sub‐optimal conditions. Optimal conditions were provided by a thymic environment with high H‐2Db density. Sub‐optimal conditions were provided by a thymic environment with decreased H‐2Db density or by an athymic environment with either high or low H‐2Db density. Whereas negative selection was still guaranteed under sub‐optimal conditions, selection and survival efficiency of cells expressing the transgenic TCR were strongly dependent on optimal conditions. These results indicated that both a thymic microenvironment and a high density of TCR‐restricting MHC molecules were needed to ensure selection and maintenance of cells expressing TCR with low affinity and hence a more diverse T cell repertoire.