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. 1988 Jul 1;168(1):195–211. doi: 10.1084/jem.168.1.195

Class I transplantation antigens in solution in body fluids and in the urine. Individuality signals to the environment

PMCID: PMC2188976  PMID: 3294330

Abstract

Classical class I transplantation antigens present in solution in the body fluids have been studied. These antigens have been found in a monomeric, soluble form in blood, lymph, and urine, and a major source is the hemopoietic system which gives rise to cells that secrete these molecules into the blood. The cell types most probably involved in their secretion are of the macrophage/dendritic cell lineage. The serum molecule is a heterodimer with a heavy chain of 39,000 mol wt associated noncovalently with beta 2-microglobulin and is present in serum at a concentration between 350 and 390 ng/ml. These molecules have a short half-life of 2.7 h and are excreted into the environment via the kidneys in the urine. In the urine, greater than 90% of the molecules are degraded into smaller fragments. This finding that normal metabolic processes lead to the excretion of classical highly polymorphic class I molecules in the urine provides a direct explanation in molecular terms of the ability of animals to identify individuals on the basis of urinary odor. Since intact class I molecules are unlikely to be the odoriferous component in the urine, two hypotheses have been suggested. Either small fragments of class I molecules are detected or the molecule acts as a carrier that transports volatiles from the serum into the urine where they are released, giving rise to the class I-associated odor.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BRUCE H. M. An exteroceptive block to pregnancy in the mouse. Nature. 1959 Jul 11;184:105–105. doi: 10.1038/184105a0. [DOI] [PubMed] [Google Scholar]
  2. Beauchamp G. K., Yamazaki K., Boyse E. A. The chemosensory recognition of genetic individuality. Sci Am. 1985 Jul;253(1):86–92. doi: 10.1038/scientificamerican0785-86. [DOI] [PubMed] [Google Scholar]
  3. Bevan M. J., Fink P. J. The influence of thymus H-2 antigens on the specificity of maturing killer and helper cells. Immunol Rev. 1978;42:3–19. doi: 10.1111/j.1600-065x.1978.tb00256.x. [DOI] [PubMed] [Google Scholar]
  4. Brown R. E., Singh P. B., Roser B. The major histocompatibility complex and the chemosensory recognition of individuality in rats. Physiol Behav. 1987;40(1):65–73. doi: 10.1016/0031-9384(87)90186-7. [DOI] [PubMed] [Google Scholar]
  5. Callahan G. N., Ferrone S., Allison J. P., Reisfeld R. A. Detection of H-2 antigens in serum. Transplantation. 1975 Nov;20(5):431–433. doi: 10.1097/00007890-197511000-00014. [DOI] [PubMed] [Google Scholar]
  6. Callahan G. N., Ferrone S., Poulik M. D., Reisfeld R. A., Klein J. Characterization of Ia antigens in mouse serum. J Immunol. 1976 Oct;117(4):1351–1355. [PubMed] [Google Scholar]
  7. Cosman D., Kress M., Khoury G., Jay G. Tissue-specific expression of an unusual H-2 (class I)-related gene. Proc Natl Acad Sci U S A. 1982 Aug;79(16):4947–4951. doi: 10.1073/pnas.79.16.4947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Diamond A. G., Larkins A. P., Wright B., Ellis S. T., Butcher G. W., Howard J. C. The alloantigenic organization of RT1Aa, a class I major histocompatibility complex molecule of the rat. Eur J Immunol. 1984 May;14(5):405–412. doi: 10.1002/eji.1830140505. [DOI] [PubMed] [Google Scholar]
  9. Dominic C. J. Observations on the reproductive pheromones of mice. I. Source. J Reprod Fertil. 1966 Jun;11(3):407–414. doi: 10.1530/jrf.0.0110407. [DOI] [PubMed] [Google Scholar]
  10. Duncan W. R., Wakeland E. K., Klein J. Heterozygosity of H-2 loci in wild mice. Nature. 1979 Oct 18;281(5732):603–605. doi: 10.1038/281603a0. [DOI] [PubMed] [Google Scholar]
  11. Ekins R. P. Radioimmunoassay and saturation analysis. Basic principles and theory. Br Med Bull. 1974 Jan;30(1):3–11. doi: 10.1093/oxfordjournals.bmb.a071163. [DOI] [PubMed] [Google Scholar]
  12. Ford W. L., Burr W., Simonsen M. A lymph node weight assay for the graft-versus-host activity of rat lymphoid cells. Transplantation. 1970 Sep;10(3):258–266. doi: 10.1097/00007890-197009000-00007. [DOI] [PubMed] [Google Scholar]
  13. Hart D. N., Fabre J. W. Problems in the use of erythrocytes for RT1.A typing studies, probably due to quantitative differences in RT1.A antigen expression in different strains. Transplant Proc. 1981 Jun;13(2):1329–1332. [PubMed] [Google Scholar]
  14. Heusser C., Boesman M., Nordin J. H., Isliker H. Effect of chemical and enzymatic radioiodination on in vitro human Clq activities. J Immunol. 1973 Mar;110(3):820–828. [PubMed] [Google Scholar]
  15. Hood L., Steinmetz M., Malissen B. Genes of the major histocompatibility complex of the mouse. Annu Rev Immunol. 1983;1:529–568. doi: 10.1146/annurev.iy.01.040183.002525. [DOI] [PubMed] [Google Scholar]
  16. Kamada N., Davies H. S., Roser B. Reversal of transplantation immunity by liver grafting. Nature. 1981 Aug 27;292(5826):840–842. doi: 10.1038/292840a0. [DOI] [PubMed] [Google Scholar]
  17. Klein J. The major histocompatibility complex of the mouse. Science. 1979 Feb 9;203(4380):516–521. doi: 10.1126/science.104386. [DOI] [PubMed] [Google Scholar]
  18. Krangel M. S. Secretion of HLA-A and -B antigens via an alternative RNA splicing pathway. J Exp Med. 1986 May 1;163(5):1173–1190. doi: 10.1084/jem.163.5.1173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Krangel M. S. Unusual RNA splicing generates a secreted form of HLA-A2 in a mutagenized B lymphoblastoid cell line. EMBO J. 1985 May;4(5):1205–1210. doi: 10.1002/j.1460-2075.1985.tb03761.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kress M., Cosman D., Khoury G., Jay G. Secretion of a transplantation-related antigen. Cell. 1983 Aug;34(1):189–196. doi: 10.1016/0092-8674(83)90149-6. [DOI] [PubMed] [Google Scholar]
  21. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  22. Maloy W. L., Coligan J. E., Barra Y., Jay G. Detection of a secreted form of the murine H-2 class I antigen with an antibody against its predicted carboxyl terminus. Proc Natl Acad Sci U S A. 1984 Feb;81(4):1216–1220. doi: 10.1073/pnas.81.4.1216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Marchlewska-Koj A. Pregnancy block elicited by urinary proteins of male mice. Biol Reprod. 1977 Dec;17(5):729–732. doi: 10.1095/biolreprod17.5.729. [DOI] [PubMed] [Google Scholar]
  24. Parham P. Purification of immunologically active HLA-A and -B antigens by a series of monoclonal antibody columns. J Biol Chem. 1979 Sep 25;254(18):8709–8712. [PubMed] [Google Scholar]
  25. Roser B., Dorsch S. The cellular basis of transplantation tolerance in the rat. Immunol Rev. 1979;46:55–86. doi: 10.1111/j.1600-065x.1979.tb00284.x. [DOI] [PubMed] [Google Scholar]
  26. Singh P. B., Brown R. E., Roser B. MHC antigens in urine as olfactory recognition cues. Nature. 1987 May 14;327(6118):161–164. doi: 10.1038/327161a0. [DOI] [PubMed] [Google Scholar]
  27. Spencer S. C., Fabre J. W. Water-soluble form of RT1.A class I MHC molecules in the kidney and liver of the rat. Immunogenetics. 1987;25(2):91–98. doi: 10.1007/BF00364273. [DOI] [PubMed] [Google Scholar]
  28. Sundberg H., Døving K., Novikov S., Ursin H. A method for studying responses and habituation to odors in rats. Behav Neural Biol. 1982 Jan;34(1):113–119. doi: 10.1016/s0163-1047(82)91501-1. [DOI] [PubMed] [Google Scholar]
  29. Vandenbergh J. G., Finlayson J. S., Dobrogosz W. J., Dills S. S., Kost T. A. Chromatographic separation of puberty accelerating pheromone from male mouse urine. Biol Reprod. 1976 Sep;15(2):260–265. doi: 10.1095/biolreprod15.2.260. [DOI] [PubMed] [Google Scholar]
  30. Vincent C., Revillard J. P. Characterization of molecules bearing HLA determinants in serum and urine. Transplant Proc. 1979 Jun;11(2):1301–1302. [PubMed] [Google Scholar]
  31. Yamazaki K., Beauchamp G. K., Bard J., Thomas L., Boyse E. A. Chemosensory recognition of phenotypes determined by the Tla and H-2K regions of chromosome 17 of the mouse. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7828–7831. doi: 10.1073/pnas.79.24.7828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Yamazaki K., Beauchamp G. K., Matsuzaki O., Kupniewski D., Bard J., Thomas L., Boyse E. A. Influence of a genetic difference confined to mutation of H-2K on the incidence of pregnancy block in mice. Proc Natl Acad Sci U S A. 1986 Feb;83(3):740–741. doi: 10.1073/pnas.83.3.740. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Yamazaki K., Beauchamp G. K., Thomas L., Boyse E. A. The hematopoietic system is a source of odorants that distinguish major histocompatibility types. J Exp Med. 1985 Oct 1;162(4):1377–1380. doi: 10.1084/jem.162.4.1377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Yamazaki K., Beauchamp G. K., Wysocki C. J., Bard J., Thomas L., Boyse E. A. Recognition of H-2 types in relation to the blocking of pregnancy in mice. Science. 1983 Jul 8;221(4606):186–188. doi: 10.1126/science.6857281. [DOI] [PubMed] [Google Scholar]
  35. Yamazaki K., Boyse E. A., Miké V., Thaler H. T., Mathieson B. J., Abbott J., Boyse J., Zayas Z. A., Thomas L. Control of mating preferences in mice by genes in the major histocompatibility complex. J Exp Med. 1976 Nov 2;144(5):1324–1335. doi: 10.1084/jem.144.5.1324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Zimmermann F. A., Butcher G. W., Davies H. S., Brons G., Kamada N., Türel O. Techniques for orthotopic liver transplantation in the rat and some studies of the immunologic responses to fully allogeneic liver grafts. Transplant Proc. 1979 Mar;11(1):571–577. [PubMed] [Google Scholar]
  37. Zinkernagel R. M., Doherty P. C. MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol. 1979;27:51–177. doi: 10.1016/s0065-2776(08)60262-x. [DOI] [PubMed] [Google Scholar]
  38. van Rood J. J., van Leeuwen A., van Santen M. C. Anti HL-A2 inhibitor in normal human serum. Nature. 1970 Apr 25;226(5243):366–367. doi: 10.1038/226366a0. [DOI] [PubMed] [Google Scholar]

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