Structurally distinct T cell receptor complexes on developmentally distinct T cell populations in severe combined immunodeficiency mice expressing a TCR beta transgene.
T cell differentiation and TCR expression were assessed in severe combined immunodeficiency (SCID) mice possessing an already rearranged TCRV beta 8 transgene. Unlike nontransgenic SCID mice, TCRV beta 8-transgenic SCID mice contained a broad spectrum of T cell populations, including both immature thymocytes and mature T cells. In TCRV beta 8-transgenic SCID mice, immature CD4-CD8- and CD4+CD8+ thymocytes expressed surface TCR complexes structurally distinct from those expressed by mature single-positive T cells. Immature CD4+CD8+ thymocytes expressed surface TCR beta chains without a clonotypic TCR partner chain and largely without associated CD3 components. In contrast, mature single-positive T cells expressed fully assembled surface TCR complexes containing disulfide-linked heterodimers consisting of transgenic TCR beta chains and endogenous TCR alpha chains. The surface TCR complexes on mature T cells were associated with CD3 components and were competent to transduce TCR-mediated proliferative signals. Thus, T cells at different stages of development in TCRV beta 8-transgenic SCID mice express structurally distinct surface TCR complexes, demonstrating that the developmental stage achieved by T cells in these mice is related to the structure of the surface TCR complexes they express. Indeed, the present results indicate that successful differentiation into single-positive T cells requires surface expression of fully assembled TCR complexes.
Shores
E W
EW
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Nakayama
T
T
Wiest
D L
DL
Takahama
Y
Y
Sharrow
S
S
Singer
A
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis; D002454:Cell Differentiation; D005434:Flow Cytometry; D051379:Mice; D016513:Mice, SCID / Q000276:immunology*; D008822:Mice, Transgenic; D010716:Phosphatidylinositols / Q000737:chemistry; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology
D016827:CD8 Antigens; D010716:Phosphatidylinositols; D016693:Receptors, Antigen, T-Cell, alpha-beta