Alternative Splicing of Class Ib Major Histocompatibility Complex Transcripts in vivo Leads to the Expression of Soluble Qa-2 Molecules in Murine Blood

• Published in: Proceedings of the National Academy of Sciences - PNAS 1994-03, Vol.91 (5), p.1883-1887
• Main Authors: Tabaczewski, Piotr, Shirwan, Haval, Lewis, Keith, Stroynowski, Iwona
• Format: Article
• Language: English
• Subjects: Alternative Splicing; Amino Acid Sequence; Animals; Antibody Specificity; Antigens; Antiserum; Base Sequence; Biochemistry; Biological and medical sciences; Blood; Concanavalin A - pharmacology; DNA, Complementary - genetics; Exons; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Histocompatibility antigens (hla, h-2 and other systems); Histocompatibility Antigens Class I - blood; Histocompatibility Antigens Class I - genetics; Immunity (Disease); In Vitro Techniques; L cells; Major Histocompatibility Complex; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Molecular immunology; Molecular Sequence Data; Molecules; Poly I-C - pharmacology; Proteins; Rabbits; Rodents; Solubility; Spleen - immunology; Splenocytes; T lymphocytes; Transcription, Genetic
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.5.1883

Class Ib Qa-2 molecules are expressed in tissue culture cells as ≈40-kDa membrane-bound, glycophosphatidylinositol-linked antigens and as ≈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.