CD4 expression is differentially required for deletion of MLS-1a-reactive T cells.
Clonal deletion of thymocytes expressing potentially self-reactive T cell receptors (TCRs) occurs during thymocyte ontogeny. Mice deficient for CD4 expression provide a unique model system to study the contribution of the CD4 molecule in negative selection of T cells reactive against the major histocompatibility complex class II-associated retroviral self-superantigen, Mls-1a. In the presence of Mls-1a determinants, mature CD8+ T cells expressing V beta 6, 8.1, and 9 were deleted in CD4-deficient mice, thus demonstrating that TCR affinity for Mls-1a is sufficient for deletion and that a signal through CD4 was not required. However, in instances where the TCR affinity for Mls-1a is low, as in the case of V beta 7+ T cells, CD4 expression was required for clonal deletion. These results demonstrate that for Mls-1a-mediated clonal deletion of T cells, the requirement for the accessory or coreceptor function of CD4 depends on the affinity of the TCR.
Wallace
V A
VA
Department of Medical Biophysics and Immunology, University of Toronto, Ontario, Canada.
Rahemtulla
A
A
Timms
E
E
Penninger
J
J
Mak
T W
TW
D000818:Animals; D015704:CD4 Antigens / Q000032:analysis / Q000502:physiology*; D006183:H-2 Antigens / Q000032:analysis; D051379:Mice; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D016747:Minor Lymphocyte Stimulatory Antigens / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
D015704:CD4 Antigens; D006183:H-2 Antigens; D016747:Minor Lymphocyte Stimulatory Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta