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 approximately 40-kDa membrane-bound, glycophosphatidylinositol-linked antigens and as approximately 39-kDa soluble polypeptides. Recently, alternative splicing events which delete exon 5 from a portion of Qa-2 transcripts were demonstrated to give rise to truncated secreted Qa-2 molecules in transfected cell lines. To determine whether this mechanism operates in vivo and to find out whether Qa-2 can be detected in soluble form in circulation, murine blood samples were analyzed. Critical to these experiments was preparation of an anti-peptide antiserum against 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 plasma contain two forms of soluble Qa-2 molecules. One form corresponds to a secreted molecule translated from transcripts from which exon 5 has been deleted; the other is derived from membrane-bound antigens or their precursors. The levels of both soluble forms of Qa-2 are inducible upon stimulation of the immune system, suggesting an immunoregulatory role for these molecules or for the mechanism leading to the reduction of cell-associated Qa-2 antigens in vivo.
Tabaczewski
P
P
Department of Microbiology, University of Texas Southwestern Medical Center at Dallas 75235-8854.
Shirwan
H
H
Lewis
K
K
Stroynowski
I
I
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D001483:Base Sequence; D003208:Concanavalin A / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D015395:Histocompatibility Antigens Class I / Q000097:blood* / Q000235:genetics*; D066298:In Vitro Techniques; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011070:Poly I-C / Q000494:pharmacology; D011817:Rabbits; D012995:Solubility; D013154:Spleen / Q000276:immunology; D014158:Transcription, Genetic
D018076:DNA, Complementary; D015395:Histocompatibility Antigens Class I; C032907:Q surface antigens; D003208:Concanavalin A; D011070:Poly I-C