Failure of T cell receptor Vβ negative selection in an athymic environment

• Published in: Science (American Association for the Advancement of Science) 1989-11, Vol.246 (4933), p.1041-1044
• Main Authors: HODES, R. J, SHARROW, S. O, SOLOMON, A
• Format: Article
• Language: English
• Subjects: Animals; Antigen receptors, T cell; Antigens, Differentiation, T-Lymphocyte - genetics; Biological and medical sciences; Chromosome Deletion; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression; Genetic aspects; Genetics; Immunobiology; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Macromolecular Substances; Major Histocompatibility Complex; Mice; Mice, Inbred BALB C - immunology; Mice, Inbred Strains - immunology; Mice, Nude - immunology; Nude mouse; Receptors; Receptors, Antigen, T-Cell - genetics; Reference Values; Species Specificity; T cell antigen receptors; T cells; T-Lymphocytes - immunology; Thymus; Thymus gland
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.2587987

The mature T cell receptor (TCR) repertoire is the result of selection events during T cell development. Previous assessment of TCR beta-chain selection with serologic and molecular probes demonstrated both positive and negative selection. Although this work suggested a critical role for the thymus, no direct assessment has been made of the requirement for a thymus in TCR V beta selection. A comparison of TCR V beta expression in four different congenic pairs of normal and nu/nu (athymic) mice indicated that the normal V beta deletions associated with tolerance to self minor lymphocyte stimulating (Mlsc) antigens or to self major histocompatibility complex (MHC)-encoded E alpha E beta products did not occur in most athymic mice. Thus, the thymus has a critical role in mediating self tolerance by negative selection.