Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1996 Oct 1;98(7):1613–1618. doi: 10.1172/JCI118955

Major histocompatibility complex class I molecule expression is normal on peripheral blood lymphocytes from patients with insulin-dependent diabetes mellitus.

W Hao 1, P Gladstone 1, S Engardt 1, C Greenbaum 1, J P Palmer 1
PMCID: PMC507594  PMID: 8833910

Abstract

Recent work from one laboratory has shown, in both nonobese diabetic mice and humans, an association between insulin-dependent diabetes mellitus (IDDM) and quantitative difference in MHC class I molecule expression. This reported decrease in MHC class I molecule expression is very controversial in the nonobese diabetic mouse model of IDDM, but to our knowledge, it has not been evaluated by another group in human IDDM. To evaluate this question, we studied 30 patients with IDDM and 30 age- and sex-matched normal controls. MHC class I molecule expression was measured by flow cytometry with conformational-dependent MHC class I mAbs. The mean antigen density of MHC class I molecule expression in IDDM vs. normal control is 454+/-34 vs. 440+/-28 for lymphocytes and 1,440+/-117 vs. 1,494+/- 117 for monocytes, both P > 0.05. Three conformational-dependent MHC class I antibodies showed consistent results. To estimate the biological variation of MHC class I molecule expression in normal controls, we also studied 10 age- and sex-matched normal control pairs. Using X +/-SD of the percentage difference of mean antigen density in the normal control pairs as our definition of normal, we found that 70% (21/30) of IDDM patients had normal, 13% (4/30) of IDDM patients had decreased, and 17% (5/30) of IDDM patients had increased MHC class I molecule expression on lymphocytes. All IDDM patients showed normal MHC class I expression on monocytes. In conclusion, we find that there is no consistent decrease in MHC class I molecule expression on either lymphocytes or monocytes from patients with IDDM. The MHC class I molecule expression observed in IDDM patients is largely within the expected biological variation of MHC class I molecule expression that has been observed in normal controls.

Full Text

The Full Text of this article is available as a PDF (143.1 KB).

Selected References

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

  1. Auffray C., Strominger J. L. Molecular genetics of the human major histocompatibility complex. Adv Hum Genet. 1986;15:197–247. doi: 10.1007/978-1-4615-8356-1_4. [DOI] [PubMed] [Google Scholar]
  2. Bjorkman P. J., Parham P. Structure, function, and diversity of class I major histocompatibility complex molecules. Annu Rev Biochem. 1990;59:253–288. doi: 10.1146/annurev.bi.59.070190.001345. [DOI] [PubMed] [Google Scholar]
  3. Deverson E. V., Gow I. R., Coadwell W. J., Monaco J. J., Butcher G. W., Howard J. C. MHC class II region encoding proteins related to the multidrug resistance family of transmembrane transporters. Nature. 1990 Dec 20;348(6303):738–741. doi: 10.1038/348738a0. [DOI] [PubMed] [Google Scholar]
  4. Faustman D., Li X. P., Lin H. Y., Fu Y. E., Eisenbarth G., Avruch J., Guo J. Linkage of faulty major histocompatibility complex class I to autoimmune diabetes. Science. 1991 Dec 20;254(5039):1756–1761. doi: 10.1126/science.1763324. [DOI] [PubMed] [Google Scholar]
  5. Faustman D., Li X., Lin H. Y., Huang R., Guo J. Response. Science. 1992 Jun 26;256(5065):1830–1831. doi: 10.1126/science.256.5065.1830. [DOI] [PubMed] [Google Scholar]
  6. Fling S. P., Arp B., Pious D. HLA-DMA and -DMB genes are both required for MHC class II/peptide complex formation in antigen-presenting cells. Nature. 1994 Apr 7;368(6471):554–558. doi: 10.1038/368554a0. [DOI] [PubMed] [Google Scholar]
  7. Fu Y., Nathan D. M., Li F., Li X., Faustman D. L. Defective major histocompatibility complex class I expression on lymphoid cells in autoimmunity. J Clin Invest. 1993 May;91(5):2301–2307. doi: 10.1172/JCI116459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gaskins H. R., Monaco J. J., Leiter E. H. Expression of intra-MHC transporter (Ham) genes and class I antigens in diabetes-susceptible NOD mice. Science. 1992 Jun 26;256(5065):1826–1831. doi: 10.1126/science.1352067. [DOI] [PubMed] [Google Scholar]
  9. Gladstone P., Fueresz L., Pious D. Gene dosage and gene expression in the HLA region: evidence from deletion variants. Proc Natl Acad Sci U S A. 1982 Feb;79(4):1235–1239. doi: 10.1073/pnas.79.4.1235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Huang R., Guo J., Li X., Faustman D. L. Elimination of self-peptide major histocompatibility complex class I reactivity in NOD and beta 2-microglobulin-negative mice. Diabetes. 1995 Sep;44(9):1114–1120. doi: 10.2337/diab.44.9.1114. [DOI] [PubMed] [Google Scholar]
  11. Leiter E. H., Christianson G. J., Serreze D. V., Ting A. T., Worthen S. M. MHC antigen induction by interferon gamma on cultured mouse pancreatic beta cells and macrophages. Genetic analysis of strain differences and discovery of an "occult" class I-like antigen in NOD/Lt mice. J Exp Med. 1989 Oct 1;170(4):1243–1262. doi: 10.1084/jem.170.4.1243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Li F., Guo J., Fu Y., Yan G., Faustman D. Abnormal class I assembly and peptide presentation in the nonobese diabetic mouse. Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11128–11132. doi: 10.1073/pnas.91.23.11128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ljunggren H. G., Stam N. J., Ohlén C., Neefjes J. J., Höglund P., Heemels M. T., Bastin J., Schumacher T. N., Townsend A., Kärre K. Empty MHC class I molecules come out in the cold. Nature. 1990 Aug 2;346(6283):476–480. doi: 10.1038/346476a0. [DOI] [PubMed] [Google Scholar]
  14. Monaco J. J., Cho S., Attaya M. Transport protein genes in the murine MHC: possible implications for antigen processing. Science. 1990 Dec 21;250(4988):1723–1726. doi: 10.1126/science.2270487. [DOI] [PubMed] [Google Scholar]
  15. Neefjes J. J., Momburg F., Hämmerling G. J. Selective and ATP-dependent translocation of peptides by the MHC-encoded transporter. Science. 1993 Aug 6;261(5122):769–771. doi: 10.1126/science.8342042. [DOI] [PubMed] [Google Scholar]
  16. Pearce R. B., Trigler L., Svaasand E. K., Chen H. M., Peterson C. M. Levels of Tap-1 and Tap-2 mRNA and expression of Kd and Db on splenic lymphocytes are normal in NOD mice. Diabetes. 1995 May;44(5):572–579. doi: 10.2337/diab.44.5.572. [DOI] [PubMed] [Google Scholar]
  17. Rock K. L., Gramm C., Benacerraf B. Low temperature and peptides favor the formation of class I heterodimers on RMA-S cells at the cell surface. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4200–4204. doi: 10.1073/pnas.88.10.4200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Spies T., Bresnahan M., Bahram S., Arnold D., Blanck G., Mellins E., Pious D., DeMars R. A gene in the human major histocompatibility complex class II region controlling the class I antigen presentation pathway. Nature. 1990 Dec 20;348(6303):744–747. doi: 10.1038/348744a0. [DOI] [PubMed] [Google Scholar]
  19. Trowsdale J., Hanson I., Mockridge I., Beck S., Townsend A., Kelly A. Sequences encoded in the class II region of the MHC related to the 'ABC' superfamily of transporters. Nature. 1990 Dec 20;348(6303):741–744. doi: 10.1038/348741a0. [DOI] [PubMed] [Google Scholar]
  20. Wicker L. S., Podolin P. L., Fischer P., Sirotina A., Boltz R. C., Jr, Peterson L. B. Expression of intra-MHC transporter (Ham) genes and class I antigens in diabetes-susceptible NOD mice. Science. 1992 Jun 26;256(5065):1828–1831. doi: 10.1126/science.1319611. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES