The amyloid precursor-like protein 2 and the adenoviral E3/19K protein both bind to a conformational site on H-2Kd and regulate H-2Kd expression.

A protein of unknown physiological function, called amyloid precursor-like protein 2 (APLP2), forms an association with the murine class I molecule K(d) that is up-regulated by the presence of the adenoviral protein E3/19K. We have extended these findings to show that APLP2 and E3/19K associate preferentially with folded K(d) and not with the open form. APLP2 was detectable at the cell surface, but its surface expression was not up-regulated by the concurrent expression of K(d). Experimental down-regulation of APLP2 expression caused a consistent increase in the surface expression of K(d), indicating that APLP2 normally reduces K(d) surface expression. These data suggest a role for APLP2 in controlling the maturation of major histocompatibility complex class I molecules.