Abstract
Recent studies have demonstrated aberrant expression and topographical heterogeneity of HLA Class I and Class II antigens in tissues of patients with certain immunologic or neoplastic diseases. Current information about the expression of HLA antigens by normal and diseased hepatocytes is controversial. We analyzed the HLA antigenic profile of 4 normal fetal livers, 5 normal adult livers, 7 cases of chronic hepatitis B virus (HBV) infection, 14 cases of cirrhosis of various etiologies, 11 hepatic neoplasms, and 5 continuous cell lines derived from hepatic tumors. The specimens were tested by the indirect fluorescent antibody method with a panel of monoclonal antibodies to distinct monomorphic determinants of HLA Class I and Class II antigens and to beta 2-microglobulin. HLA Cells I antigens were not detected on normal fetal and adult hepatocytes, but were displayed on the plasma membrane of hepatocytes in the majority of all hepatic diseases tested and of the 5 hepatic tumor cell lines. There was a significant correlation between the expression of HLA Class I antigens on hepatocytes and the intensity of intralobular inflammation. Double immunofluorescent staining of livers infected with hepatitis B virus demonstrated simultaneous expression of HLA Class I antigens and HBsAg or HBcAg only in a small percentage of hepatocytes, suggesting lack of a specific association between HLA Class I and these viral antigens. HLA Class II antigens were not detected on hepatocytes from any of the liver diseases tested but were expressed by one of the 5 liver carcinoma cell lines analyzed. These findings confirm that HLA Class I antigens are not detectable within the limits of several immunohistochemical methods on normal hepatocytes and suggest that injury by a variety of factors directly or indirectly leads to induction of these antigens on the plasma membrane of hepatocytes.
Full text
PDF






Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aden D. P., Fogel A., Plotkin S., Damjanov I., Knowles B. B. Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line. Nature. 1979 Dec 6;282(5739):615–616. doi: 10.1038/282615a0. [DOI] [PubMed] [Google Scholar]
- Alexander J. J., Bey E. M., Geddes E. W., Lecatsas G. Establishment of a continuously growing cell line from primary carcinoma of the liver. S Afr Med J. 1976 Dec 18;50(54):2124–2128. [PubMed] [Google Scholar]
- Barbatis C., Woods J., Morton J. A., Fleming K. A., McMichael A., McGee J. O. Immunohistochemical analysis of HLA (A, B, C) antigens in liver disease using a monoclonal antibody. Gut. 1981 Dec;22(12):985–991. doi: 10.1136/gut.22.12.985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Daar A. S., Fuggle S. V., Fabre J. W., Ting A., Morris P. J. The detailed distribution of HLA-A, B, C antigens in normal human organs. Transplantation. 1984 Sep;38(3):287–292. doi: 10.1097/00007890-198409000-00018. [DOI] [PubMed] [Google Scholar]
- Dausset J., Contu L. Is the MHC a general self-recognition system playing a major unifying role in an organism? Hum Immunol. 1980 Jul;1(1):5–17. doi: 10.1016/0198-8859(80)90004-x. [DOI] [PubMed] [Google Scholar]
- Ferrone S., Allison J. P., Pellegrino M. A. Human DR (Ia-like) antigens: biological and molecular profile. Contemp Top Mol Immunol. 1978;7:239–281. doi: 10.1007/978-1-4757-0779-3_8. [DOI] [PubMed] [Google Scholar]
- Fleming K. A., McMichael A., Morton J. A., Woods J., McGee J. O. Distribution of HLA class 1 antigens in normal human tissue and in mammary cancer. J Clin Pathol. 1981 Jul;34(7):779–784. doi: 10.1136/jcp.34.7.779. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gerber M. A., Garfinkel E., Hirschman S. Z., Thung S. N., Panagiotatos T. Immune and enzyme histochemical studies of a human hepatocellular carcinoma cell line producing hepatitis B surface antigen. J Immunol. 1981 Mar;126(3):1085–1089. [PubMed] [Google Scholar]
- Hanafusa T., Pujol-Borrell R., Chiovato L., Russell R. C., Doniach D., Bottazzo G. F. Aberrant expression of HLA-DR antigen on thyrocytes in Graves' disease: relevance for autoimmunity. Lancet. 1983 Nov 12;2(8359):1111–1115. doi: 10.1016/s0140-6736(83)90628-1. [DOI] [PubMed] [Google Scholar]
- Lautenschlager I., Taskinen E., Inkinen K., Lehto V. P., Virtanen I., Häyry P. Distribution of the major histocompatibility complex antigens on different cellular components of human liver. Cell Immunol. 1984 Apr 15;85(1):191–200. doi: 10.1016/0008-8749(84)90289-2. [DOI] [PubMed] [Google Scholar]
- McMichael A. J. HLA restriction of human cytotoxic T cells. Springer Semin Immunopathol. 1980 May;3(1):3–22. doi: 10.1007/BF00199923. [DOI] [PubMed] [Google Scholar]
- Montano L., Miescher G. C., Goodall A. H., Wiedmann K. H., Janossy G., Thomas H. C. Hepatitis B virus and HLA antigen display in the liver during chronic hepatitis B virus infection. Hepatology. 1982 Sep-Oct;2(5):557–561. doi: 10.1002/hep.1840020508. [DOI] [PubMed] [Google Scholar]
- Natali P. G., Bigotti A., Nicotra M. R., Viora M., Manfredi D., Ferrone S. Distribution of human Class I (HLA-A,B,C) histocompatibility antigens in normal and malignant tissues of nonlymphoid origin. Cancer Res. 1984 Oct;44(10):4679–4687. [PubMed] [Google Scholar]
- Natali P. G., De Martino C., Quaranta V., Nicotra M. R., Frezza F., Pellegrino M. A., Ferrone S. Expression of Ia-like antigens in normal human nonlymphoid tissues. Transplantation. 1981 Jan;31(1):75–78. doi: 10.1097/00007890-198101000-00017. [DOI] [PubMed] [Google Scholar]
- Parham P., Barnstable C. J., Bodmer W. F. Use of a monoclonal antibody (W6/32) in structural studies of HLA-A,B,C, antigens. J Immunol. 1979 Jul;123(1):342–349. [PubMed] [Google Scholar]
- Parr E. L. Diversity of expression of H-2 antigens on mouse liver cells demonstrated by immunoferritin labeling. Transplantation. 1979 Jan;27(1):45–48. doi: 10.1097/00007890-197901000-00012. [DOI] [PubMed] [Google Scholar]
- Pollack M. S., Livingston P. O., Fogh J., Carey T. E., Oettgen H. F., Dupont B. Genetically appropriate expression of HLA and DR (IA) alloantigens on human melanoma cell lines. Tissue Antigens. 1980 Mar;15(3):249–256. doi: 10.1111/j.1399-0039.1980.tb00915.x. [DOI] [PubMed] [Google Scholar]
- Ponder B. A., Wilkinson M. M., Wood M., Westwood J. H. Immunohistochemical demonstration of H2 antigens in mouse tissue sections. J Histochem Cytochem. 1983 Jul;31(7):911–919. doi: 10.1177/31.7.6343482. [DOI] [PubMed] [Google Scholar]
- Preble O. T., Friedman R. M. Interferon-induced alterations in cells: relevance to viral and nonviral diseases. Lab Invest. 1983 Jul;49(1):4–18. [PubMed] [Google Scholar]
- Quaranta V., Walker L. E., Pellegrino M. A., Ferrone S. Purification of immunologically functional subsets of human Ia-like antigens on a monoclonal antibody (Q5/13) immunoadsorbent. J Immunol. 1980 Oct;125(4):1421–1425. [PubMed] [Google Scholar]
- Saunders D. A., Beals T. F., Schultz J. S. Qualitative and quantitative evaluation of indirect immunofluorescent H-2 stain on tissue sections. Tissue Antigens. 1979 Aug;14(2):73–85. doi: 10.1111/j.1399-0039.1979.tb00826.x. [DOI] [PubMed] [Google Scholar]
- Strominger J. L., Cresswell P., Grey H., Humphreys R. E., Mann D., McCuneJ, Parham P., Robb R., Sanderson A. R., Springer T. A. The immunoglobulin-like structure of human histocompatibility antigens. Transplant Rev. 1974;21(0):126–143. doi: 10.1111/j.1600-065x.1974.tb01549.x. [DOI] [PubMed] [Google Scholar]
- Thung S. N., Gerber M. A., Sarno E., Popper H. Distribution of five antigens in hepatocellular carcinoma. Lab Invest. 1979 Aug;41(2):101–105. [PubMed] [Google Scholar]
- Williams K. A., Hart D. N., Fabre J. W., Morris P. J. Distribution and quantitation of HLA-ABC and DR (Ia) antigens on human kidney and other tissues. Transplantation. 1980 Apr;29(4):274–279. doi: 10.1097/00007890-198004000-00002. [DOI] [PubMed] [Google Scholar]
- Wilson B. S., Herzig M. A., Lloyd R. V. Immunoperoxidase staining for Ia-like antigens in paraffin-embedded tissues from human melanoma and lung carcinoma. Am J Pathol. 1984 Apr;115(1):102–108. [PMC free article] [PubMed] [Google Scholar]