Most mice display two conventional major histocompatibility complex class II isotypes, A and E. Several A+E− strains have been observed, but never any that are A-E+. Because of this and because of hints from several lines of functional analysis, it has been proposed that the two isotypes might not operate equivalently. This proposition has not been directly testable until now because of the lack of an E-only strain. We report the production of such mice, exploiting previously created class II-transgenic and dass II-“knock-out” lines. A+E−, A−E−, and A−E+ littermates have been compared by a number of parameters. We find that E and A molecules are, for the most part, functionally equivalent. However, subtle differences are seen in their ability to engage CD4 molecules on immature thymocytes, and in the profile of receptors on T cells selected into the periphery.
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