Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1985 Jul;76(1):381–385. doi: 10.1172/JCI111974

A defect in the regulation of major histocompatibility complex class II gene expression in human HLA-DR negative lymphocytes from patients with combined immunodeficiency syndrome.

B Lisowska-Grospierre, D J Charron, C de Préval, A Durandy, C Griscelli, B Mach
PMCID: PMC423788  PMID: 3860509

Abstract

Patients with an autosomal recessive combined immunodeficiency are characterized by an HLA negative phenotype of activated T and B lymphocytes. To determine the molecular basis of this syndrome we have studied the biosynthesis of class I and II antigens and the expression of relevant genes in these patients. The synthesis of the HLA A, B, and C heavy chain is markedly decreased, while beta 2 microglobulin is made in normal amounts. Biosynthesis of HLA-DR alpha-chain and beta-chain is abolished in the lymphocytes of these patients and there is a total absence of mRNA for either alpha-chains or beta-chains of HLA-DR. This indicates that the lack of class II antigen on these lymphocytes results from a block in the expression of HLA-DR genes. The Ii-chain, the invariant polypeptide associated intracellularly with HLA-DR, and its mRNA are made in normal amounts. Since the structural genes coding for class II polypeptides do not seem to be affected, the reported genetic defect in the patients concerns the regulation of the expression of HLA-DR genes.

Full text

PDF

Images in this article

382Image
on p.382
383Image
on p.383
383Image
on p.383
384Image
on p.384
384Image
on p.384
384Image
on p.384

Selected References

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

  1. Accolla R. S. Human B cell variants immunoselected against a single Ia antigen subset have lost expression of several Ia antigen subsets. J Exp Med. 1983 Mar 1;157(3):1053–1058. doi: 10.1084/jem.157.3.1053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anderson D. W., Barrett J. T. Ultrasound: a new immunosuppressant. Clin Immunol Immunopathol. 1979 Sep;14(1):18–29. doi: 10.1016/0090-1229(79)90121-1. [DOI] [PubMed] [Google Scholar]
  3. Barnstable C. J., Bodmer W. F., Brown G., Galfre G., Milstein C., Williams A. F., Ziegler A. Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens-new tools for genetic analysis. Cell. 1978 May;14(1):9–20. doi: 10.1016/0092-8674(78)90296-9. [DOI] [PubMed] [Google Scholar]
  4. Charron D. J., Lotteau V., Turmel P. Hybrid HLA-DC antigens provide molecular evidence for gene trans-complementation. Nature. 1984 Nov 8;312(5990):157–159. doi: 10.1038/312157a0. [DOI] [PubMed] [Google Scholar]
  5. Charron D. J., McDevitt H. O. Characterization of HLA-D-region antigens by two-dimensional gel electrophoresis. Molecular-genotyping. J Exp Med. 1980 Aug 1;152(2 Pt 2):18s–36s. [PubMed] [Google Scholar]
  6. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  7. Collins T., Korman A. J., Wake C. T., Boss J. M., Kappes D. J., Fiers W., Ault K. A., Gimbrone M. A., Jr, Strominger J. L., Pober J. S. Immune interferon activates multiple class II major histocompatibility complex genes and the associated invariant chain gene in human endothelial cells and dermal fibroblasts. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4917–4921. doi: 10.1073/pnas.81.15.4917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Devos R., Opsomer C., Scahill S. J., Van der Heyden J., Fiers W. Purification of recombinant glycosylated human gamma interferon expressed in transformed Chinese hamster ovary cells. J Interferon Res. 1984 Fall;4(4):461–468. doi: 10.1089/jir.1984.4.461. [DOI] [PubMed] [Google Scholar]
  9. Durandy A., Virelizier J. L., Griscelli C. Enhancement by interferon of membrane HLA antigens in patients with combined immunodeficiency with defective HLA expression. Clin Exp Immunol. 1983 Apr;52(1):173–178. [PMC free article] [PubMed] [Google Scholar]
  10. Gladstone, Pious D. Stable variants affecting B cell alloantigens in human lymphoid cells. Nature. 1978 Feb 2;271(5644):459–461. doi: 10.1038/271459a0. [DOI] [PubMed] [Google Scholar]
  11. Goyert S. M., Silver J. Isolation of I-A subregion-like molecules from subhuman primates and man. Nature. 1981 Nov 19;294(5838):266–268. doi: 10.1038/294266a0. [DOI] [PubMed] [Google Scholar]
  12. Guy K., Van Heyningen V., Cohen B. B., Deane D. L., Steel C. M. Differential expression and serologically distinct subpopulations of human Ia antigens detected with monoclonal antibodies to Ia alpha and beta chains. Eur J Immunol. 1982 Nov;12(11):942–948. doi: 10.1002/eji.1830121109. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Long E. O., Mach B., Accolla R. S. Ia-negative B-cell variants reveal a coordinate regulation in the transcription of the HLA class II gene family. Immunogenetics. 1984;19(4):349–353. doi: 10.1007/BF00345408. [DOI] [PubMed] [Google Scholar]
  15. Long E. O., Strubin M., Wake C. T., Gross N., Carrel S., Goodfellow P., Accolla R. S., Mach B. Isolation of cDNA clones for the p33 invariant chain associated with HLA-DR antigens. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5714–5718. doi: 10.1073/pnas.80.18.5714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McMaster G. K., Carmichael G. G. Analysis of single- and double-stranded nucleic acids on polyacrylamide and agarose gels by using glyoxal and acridine orange. Proc Natl Acad Sci U S A. 1977 Nov;74(11):4835–4838. doi: 10.1073/pnas.74.11.4835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Touraine J. L., Betuel H., Souillet G., Jeune M. Combined immunodeficiency disease associated with absence of cell-surface HLA-A and -B antigens. J Pediatr. 1978 Jul;93(1):47–51. doi: 10.1016/s0022-3476(78)80598-8. [DOI] [PubMed] [Google Scholar]
  18. Virelizier J. L., Perez N., Arenzana-Seisdedos F., Devos R. Pure interferon gamma enhances class II HLA antigens on human monocyte cell lines. Eur J Immunol. 1984 Jan;14(1):106–108. doi: 10.1002/eji.1830140120. [DOI] [PubMed] [Google Scholar]
  19. Volc-Platzer B., Majdic O., Knapp W., Wolff K., Hinterberger W., Lechner K., Stingl G. Evidence of HLA-DR antigen biosynthesis by human keratinocytes in disease. J Exp Med. 1984 Jun 1;159(6):1784–1789. doi: 10.1084/jem.159.6.1784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wake C. T., Long E. O., Strubin M., Gross N., Accolla R., Carrel S., Mach B. Isolation of cDNA clones encoding HLA-DR alpha chains. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6979–6983. doi: 10.1073/pnas.79.22.6979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. de Préval C., Mach B. The absence of beta 2-microglobulin in Daudi cells: active gene but inactive messenger RNA. Immunogenetics. 1983;17(2):133–140. doi: 10.1007/BF00364753. [DOI] [PubMed] [Google Scholar]

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

RESOURCES