ALTERNATIVE SPLICING OF CLASS IB MAJOR HISTOCOMPATIBILITY COMPLEX TRANSCRIPTS IN-VIVO LEADS TO THE EXPRESSION OF SOLUBLE QA-2 MOLECULES IN MURINE BLOOD

Class Ib Qa-2 molecules are expressed in tissue culture cells as appro ximate to 40-kDa membrane-bound, glycophosphatidylinositol-linked anti gens and as approximate to 39-kDa soluble polypeptides. Recently, alte rnative splicing events which delete exon 5 from a portion of Qa-2 tra nscripts were demonstrated to give rise to truncated secreted Qa-2 mol ecules in transfected cell lines. To determine whether this mechanism operates in vivo and to find out whether Qa-2 can be detected in solub le form in circulation, murine blood samples were analyzed. Critical t o these experiments was preparation of an anti peptide antiserum again st an epitope encoded by a junction of exon 4 and exon 6. We find that supernatants of splenocytes cultured in vitro as well as serum or pla sma contain two forms of soluble Qa-2 molecules. One form corresponds to a secreted molecule translated from transcripts from which exon 5 h as been deleted; the other is derived from membrane-bound antigens or their precursors. The levels of both soluble forms of Qa-2 are inducib le upon stimulation of the immune system, suggesting an immunoregulato ry role for these molecules or for the mechanism leading to the reduct ion of cell-associated Qa-2 antigens in vivo.