Abstract
H-Y antigen is defined as a male histocompatibility antigen that causes rejection of male skin grafts by female recipients of the same inbred strain of rodents. Male-specific, or H-Y antigen(s), are also detected by cytotoxic T cells and antibodies. H-Y antigen appears to be an integral part of the membrane of most male cells. In addition, H-Y antibodies detect a soluble form of H-Y that is secreted by the testis. The gene (Smcy/SMCY) coding for H-Y antigen detected by T cells has been cloned. It is expressed ubiquitously in male mice and humans, and encodes an epitope that triggers a specific T -cell response in vitro. Additional epitopes coded for by different Y-chromosomal genes are probably required in vivo for the rejection of male grafts by female hosts. The molecular nature of H-Y antigen detected by antibodies on most male cells is not yet known. Testis-secreted, soluble H-Y antigen, however, was found to be identical to Müllerian-inhibiting substance (MIS). MIS cross-reacts with H-Y antibodies and identical findings were obtained for soluble H-Y antigen and MIS, i.e., secretion by testicular Sertoli and, to a lesser degree, ovarian cells, binding to a gonad-specific receptor, induction of gonadal sex reversal in vitro and, in cattle, in vivo. H-Y antisera also detect a molecule or molecules associated with the heterogametic sex in nonmammalian vertebrates. Molecular data on this antigen or antigens are not yet available.
Similar content being viewed by others
References
Agulnik AI, Mitchell MJ, Lerner JL, Woods DR, Bishop CE (1994a) A mouse Y chromosome gene encoded by a region essential for spermatogenesis and expression of male-specific minor histocompatibility antigens. Hum Mol Genet 3:873–878
Agulnik AI, Mitchell MJ, Mattei M-G, Borsani G, Avner PA, Lerner JL, Bishop CE (1994b) A novel X gene with a widely transcribed Y-linked homologue escapes X-inactivation in mouse and human. Hum Mol Genet 3:879–884
Baarends WM, Helmond MJL van, Post M, Schoot PJCM van der, Hoogerbrugge JW, Winter JP de, Uilenbroek JTJ, Karels B, Wilming LG, Meijers JHC, Themmen APN, Grootegoed JA (1994) A novel member of the transmembrane serine/threonine kinase receptor family is specifically expressed in the gonads and in mesenchymal cells adjacent to the Müllerian duct. Development 120:189–197
Behringer RR, Cate RL, Froelick GR, Palmiter RD, Brinster RL (1990) Abnormal sexual development in transgenic mice chronically expressing Müllerian inhibiting substance. Nature 345:167–170
Brunner M, Moreira-Filho CA, Wachtel G, Wachtel SS (1984) On the secretion of H-Y antigen. Cell 37:615–619
Crumeyrolle-Arias M, Zaborski P, Scheib D, Latouche J, Aschheim P (1986) Differentiation of Sertoli-like cells in senescent ovaries of both intact and hypophysectomized rats and its relation to ovarian H-Y antigen expression. Mod Trends Aging Res 147:117–126
Eichwald EJ, Silmser CR (1955) Untitled communication. Transplant Bull 2:148–149
Ferguson-Smith MA (1966) X-Y chromosomal interchange in the aetiology of true hermaphroditism and of XX Klinefelter's syndrome. Lancet II:475–476
Gasser DL, Silvers WK (1972) Genetics and immunology of sexlinked antigens. Adv Immunol 15:215–247
Goldberg EH, Boyse EA, Bennett D, Scheid M, Carswell EA (1971) Serological demonstration of H-Y (male) antigen on mouse sperm. Nature 232:478–480
Goldberg EH, Shen F, Tokuda S (1973) Detection of H-Y (male) antigen on mouse lymph node cells by the cell to cell cytotoxicity test. Transplantation 15:334–336
Gordon RD, Simpson E, Samuelson LE (1975) In vitro cell-mediated immune responses to the male specific (H-Y) antigen in mice. J Exp Med 142:1108–1120
Imbeaud S, Faure E, Lamarre I, Mattbi M-G, Clemente N di, Tizard R, Carré-Eusèbe D, Belville C, Tragethon L, Tonkin C, Nelson J, McAuliffe M, Bidart J-M, Lababidi A, Josso N, Cate RL, Picard J-Y (1995) Insensitivity to anti-Müllerian hormone due to a mutation in the human anti-Müllerian hormone receptor. Nat Genet 11:382–388
King TR, Christianson GJ, Mitchell MJ, Bishop CE, Scott D, Ehrmann I, Simpson E, Eicher EM, Roopenian DC (1994) Deletion mapping by immunoselection against the H-Y histocompatibility antigen further resolves theSxr a region of the mouse Y chromosome and reveals complexity of theHya locus. Genomics 24:159–168
Knebelmann B, Boussin L, Guerrier D, Legeai L, Kahn A, Josso N, Picard J-Y (1991) Anti-Müllerian hormone Bruxelles: a nonsense mutation associated with the persistent Müllerian duct syndrome. Proc Natl Acad Sci USA 88:3767–3771
Koehler MR, Neuhaus D, Engel W, Schartl M, Schmid M (1995) Evidence for an unusual ZW/ZW'/ZZ sex-chromosome system in Scardinius erythrophthalmus (Pisces, Cyprinidae), as detected by cytogenetic and H-Y antigen analyses. Cytogenet Cell Genet 71:356–362
Koopman P, Gubbay J, Vivian N, Goodfellow P, Lovell-Badge R (1991) Male development of chromosomally female mice transgenic forSry. Nature 351:117–121
McLaren A (1983) Sex reversal in the mouse. Differentiation 23[Suppl]:S93-S98
McLaren A, Simpson E, Tomonari K, Chandler P, Hogg H (1984) Male sexual differentiation in mice lacking H-Y antigen. Nature 312:552–555
Mitchell MJ, Bishop CE (1992) A structural analysis of the Sxr region of the mouse Y chromosome. Genomics 12:26–34
Müller U (1981) Immunological and functional aspects of H-Y antigen. Hum Genet 58:29–33
Müller U, Urban E (1981) Reaggregation of rat gonadal cells in vitro: experiments on the function of H-Y antigen. Cytogenet Cell Genet 31:104–107
Müller U, Aschmoneit I, Zenzes MT, Wolf U (1978) Binding studies of H-Y antigen in rat tissues. Indications for a gonad-specific receptor. Hum Genet 43:151–157
Müller U, Wolf U, Siebers JW, Günther E (1979a) Evidence for a gonad-specific receptor for H-Y antigen: binding of exogenous H-Y antigen to gonadal cells is independent of β2-microglobulin. Cell 17:331–335
Müller U, Zenzes MT, Wolf U, Engel W, Weniger JP (1979b) Appearance of H-W (H-Y) antigen in the gonads of oestradiol sex-reversed male chicken embryos. Nature 280:142–144
Müller U, Wachtel SS, Jaswaney VL, Goldberg EH (1993) H-Y (SDM) antibody specifically binds Müllerian inhibiting substance. Hum Genet 91:515–518
Nakamura D, Wachtel SS, Kallman K (1984) H-Y antigen and the evolution of heterogamety. J Hered 75:353–358
Picard J-Y, Guerrier D, Kahn A, Josso N (1989) Molecular biology of anti-Müllerian hormone. In: Wachtel SS (ed) Evolutionary mechanisms in sex determination. CRC, Boca Raton, pp 209–217
Reinboth R, Mayerova A, Ebensperger C, Wolf U (1987) The occurrence of serological H-Y antigen (Sxs antigen) in the diandric protogynous wrasseCoris julis (L) (Labridae, Teleostei). Differentiation 34:13–17
Roopenian DC (1992) What are minor histocompatibility loci? A new look at an old question. Immunol Today 13:7–10
Scott DM, Dyson PJ, Simpson E (1992) A new approach to the cloning of genes encoding T-cell epitopes. Immunogenetics 36:86–94
Scott DM, Ehrmann IE, Ellis PS, Bishop CE, Agulnik AI, Simpson E, Mitchell MJ (1995) Identification of a mouse male-specific transplantation antigen, H-Y. Nature 376:695–698
Silvers WK, Gasser DL, Eicher EM (1982) H-Y antigen, serologically detectable male antigen and sex determination. Cell 28:439–440
Simpson E, Chandler P, Goulmy C, Disteche CM, Ferguson-Smith MA, Page DC (1987) Separation of the genetic loci for the HY antigen and for testis determination on human Y chromosome. Nature 326:876–878
Takahashi M, Hayashi M, Manganaro TF, Donahoe PK (1986) The ontogeny of Müllerian inhibiting substance in granulosa cells of the bovine ovarian follicle. Biol Reprod 35:447–453
Vigier B, Picard J-Y, Tran D, Legeai L, Josso N (1984a) Production of anti-Müllerian hormone: another homology between Sertoli and granulosa cells. Endocrinology 114:1315–1320
Vigier B, Tran D, Legeai L, Bézard J, Josso N (1984b) Origin of anti-Müllerian hormone in bovine freemartin fetuses. J Reprod Fertil 70:473–479
Vigier B, Watrin F, Magre S, Tran D, Josso N (1987) Purified bovine AMH induces a characteristic freemartin effect in fetal rat prospective ovaries exposed to it in vitro. Development 100:43–55
Vigier B, Forest MG, Eychenne B, Bezard J, Garrigou O, Robel P, Josso N (1989) Anti-Müllerian hormone produces endocrine sex reversal of fetal ovaries. Proc Natl Acad Sci USA 86:3684–3688
Wachtel SS (1983) H-Y antigen and the biology of sex determination. Grune and Stratton, New York
Wachtel SS, Koo GC, Boyse EA (1975) Evolutionary conservation of H-Y (“male”) antigen. Nature 254:270–272
Wachtel SS, Koo GC, Breg WR, Thaler HT, Dillard GM, Rosenthal IM, Dosik H, Gerald PS, Saenger P, New M, Lieber E, Miller OJ (1976) Serologic detection of a Y-linked gene in XX males and XX true hermaphrodites. N Engl J Med 295:750–754
Wachtel SS, Bresler PA, Koide SS (1980a) Does H-Y antigen induce the heterogametic ovary? Cell 20:859–864
Wachtel SS, Hall JL, Müller U, Chaganti RSK (1980b) Serumborne H-Y antigen in the fetal bovine freemartin. Cell 21:917–926
Wang W, Meadows LR, Haan JMM den, Sherman NE, Chen Y, Blokland E, Shabanowitz J, Agulnik AI, Hendrickson RC, Bishop CE, Hunt DF, Goulmy E, Engelhard VH (1995) Human H-Y: a male specific histocompatibility antigen derived from the SMCY protein. Science 269:1588–1590
Wolf U (1979) XY gonadal dysgenesis and the H-Y antigen. Hum Genet 47:269–277
Wolf U (1995) The molecular genetics of human sex determination. J Mol Med 73:325–331
Wolf U, Schempp W, Scherer G (1992) Molecular biology of the human Y chromosome. Rev Physiol Biochem Pharmacol 121:147–213
Zenzes MT, Müller U, Aschmoneit I, Wolf U (1978a) Studies on H-Y antigen in different cell fractions of the testis during pubescence. Immature germ cells are H-Y antigen negative. Hum Genet 45:297–303
Zenzes MT, Wolf U, Engel W (1978b) Organization in vitro of ovarian cells into testicular structures. Hum Genet 44:333–338
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Müller, U. H-Y antigens. Hum Genet 97, 701–704 (1996). https://doi.org/10.1007/BF02346175
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02346175