CD4-independent T cells impair TCR triggering of CD4-dependent T cells: a putative mechanism for T cell affinity maturation.
In vivo, T cells expressing low-affinity TCR predominate in primary, but not in secondary responses, a process referred to as T cell affinity maturation. Using CD4 dependence as a measure of the avidity of the interaction between the allospecific TCR and the alloantigen, we show that a similar process occurs in mixed lymphocyte cultures in vitro. Moreover, in coculture experiments high-avidity (CD4-independent) T cell clones inhibited the TCR internalization of low-avidity (CD4-dependent) T cell clones, whereas low-avidity T cell clones had no such effect on high-avidity T cell clones. The extent of inhibition of TCR internalization was dependent on both the avidity of the competing clone and the number of competing cells. Thus, there was a cell dose- and avidity-dependent effect on TCR internalization, an early parameter in T cell activation. These results suggest that low- and high-avidity T cell clones compete for the availability of antigen-presenting cells and that this favors the selective outgrowth of high-avidity T cell clones.
van Bergen
J
J
Leiden University Medical Center, Dept. of Immunohematology and Blood Transfusion, Leiden, The Netherlands. jv228@cam.ac.uk
Kooy
Y
Y
Koning
F
F
D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis / Q000502:physiology*; D002460:Cell Line; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*
D017252:CD3 Complex; D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell