An immune response defect due to low levels of class II cell surface expression: Analysis of antigen presentation and positive selection

The effects of quantitative differences in class II cell surface expression have been difficult to address in intact animals. This study uses several lines of H-2(s/s) mice carrying an Aβ(k) transgene that differ significantly in terms of class II cell surface expression. Due to inefficient chain pairing, mice carrying 60 to 65 copies of this transgene express only low levels of Aα(s)/Aβ(k) on the cell surface, and cell surface expression of the endogenous Aα(s)/Aβ(s) complex (and total Ia) is severely reduced (to 7-15% control levels). The significant decrease in class II cell surface expression in the thymic cortex of these mice did not affect the frequency of peripheral T cells expressing at least 10 distinct TCR Vβ chains. However, T cell proliferative responses to the Aα(s)/Aβ(s)- restricted peptide MBP 89-101 were abrogated in high copy number Aβ(k) mice. Experiments using bone marrow chimeras demonstrated that both inefficient Ag presentation and failure to positively select appropriate T cells contributed to this lack of response. Inefficient Ag presentation was clearly the dominant defect, and the density of class II cell surface expression required for positive selection appeared to be quite low.