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Coreceptor-Independent T Cell Activation in Mice Expressing MHC Class II Molecules Mutated in the CD4 Binding Domain¹

Department of Immunology, Duke University Medical Center, Durham, NC 27710

We have previously reported that efficient selection of the mature CD4⁺ T cell repertoire requires a functional interaction between the CD4 coreceptor on the developing thymocyte and the MHC class II molecule on the thymic epithelium. Mice expressing a class II protein carrying the EA137/VA142 double mutation in the CD4 binding domain develop fewer than one-third the number of CD4⁺ T cells found in wild-type mice. In this report we describe the functional characteristics of this population of CD4⁺ T cells. CD4⁺ T cells that develop under these conditions are predicted to be a CD4-independent subset of T cells, bearing TCRs of sufficient affinity for the class II ligand to undergo selection despite the absence of accessory class II-CD4 interactions. We show that CD4⁺ T cells from the class II mutant mice are indeed CD4 independent in their peripheral activation requirements. Surprisingly, we find that CD4⁺ T cells from the class II mutant mice, having been selected in the absence of a productive class II-CD4 interaction, fail to functionally engage CD4 even when subsequently provided with a wild-type class II ligand. Nevertheless, CD4⁺ T cells from EA137/VA142 class II mutant mice can respond to T-dependent Ags and support Ig isotype switching.

This article has been cited by other articles:

				Q. Wang, L. Malherbe, D. Zhang, K. Zingler, N. Glaichenhaus, and N. Killeen CD4 Promotes Breadth in the TCR Repertoire J. Immunol., October 15, 2001; 167(8): 4311 - 4320. [Abstract] [Full Text] [PDF]