Identification of a Unique Tumor-specific Antigen As a Novel Class I Major Histocompatibility Molecule

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1985 Aug 1

PMID 3860848

Citations 20

Authors

C Philipps

M McMillan

P M Flood

D B Murphy

J Forman

D Lancki

J E Womack

R S Goodenow

H Schreiber

Affiliations

Soon will be listed here.

Abstract

Cancers induced by physical or chemical carcinogens express tumor-specific antigens that are uniquely specific for any given tumor; therefore, there is a seemingly endless variety of these unique antigens. We have studied a UV-induced fibrosarcoma, designated 1591, to elucidate the obscure molecular nature and genetic origins of unique tumor-specific antigens. A monoclonal antibody raised against syngeneic 1591 tumor cells has unique tumor specificity. This tumor-specific monoclonal antibody precipitated from the tumor a 45-kDa molecule associated with a 12-kDa molecule having the pI of beta2-microglobulin. This and other evidence indicated that the 1591 tumor expresses a novel class I molecule. A 1591 variant selected for the absence of binding to the monoclonal antibody lacked the novel class I MHC molecule as well as reactivity with cytotoxic T lymphocytes specific for the 1591 tumor. Furthermore, tumor cells bearing the antigen are rejected while variants that have lost the antigen grow progressively. Fourteen of 14 host-selected progressor tumor variants lost reactivity with the monoclonal antibody and provided further evidence that this novel class I molecule is a transplantation antigen on the parental 1591 tumor required for immune rejection. The identification of a unique tumor-specific antigen as a novel class I major histocompatibility complex gene product allows us to search for the possible genetic mechanisms involved and to explore further the role such molecules play in tumor immunity and malignancy.

Citing Articles

Benchmark of tools for in silico prediction of MHC class I and class II genotypes from NGS data.

Claeys A, Merseburger P, Staut J, Marchal K, Van den Eynden J BMC Genomics. 2023; 24(1):247.

PMID: 37161318 PMC: 10170851. DOI: 10.1186/s12864-023-09351-z.

Homotypic and heterotypic associations of MHC class I molecules at the cell surface.

Ruggiero F, Springer S Curr Res Immunol. 2022; 3:85-99.

PMID: 35647522 PMC: 9133507. DOI: 10.1016/j.crimmu.2022.05.001.

Molecular characterization of novel H-2 class I molecules expressed by a C3H UV-induced fibrosarcoma.

McMillan M, Lewis K, Rovner D Proc Natl Acad Sci U S A. 1985; 82(16):5485-9.

PMID: 3860872 PMC: 391147. DOI: 10.1073/pnas.82.16.5485.

Reduced tumorigenicity of a spontaneous mouse lung carcinoma following H-2 gene transfection.

Bahler D, Frelinger J, Harwell L, Lord E Proc Natl Acad Sci U S A. 1987; 84(13):4562-6.

PMID: 3496596 PMC: 305130. DOI: 10.1073/pnas.84.13.4562.

Identification of a unique tumor antigen as rejection antigen by molecular cloning and gene transfer.

Stauss H, Van Waes C, Fink M, Starr B, Schreiber H J Exp Med. 1986; 164(5):1516-30.

PMID: 3490532 PMC: 2188451. DOI: 10.1084/jem.164.5.1516.

References

Wortzel R, Urban J, Schreiber H . Malignant growth in the normal host after variant selection in vitro with cytolytic T-cell lines. Proc Natl Acad Sci U S A. 1984; 81(7):2186-90. PMC: 345462. DOI: 10.1073/pnas.81.7.2186. View

Sharrow S, Flaherty L, Sachs D . Serologic cross-reactivity between Class I MHC molecules and an H-2-linked differentiation antigen as detected by monoclonal antibodies. J Exp Med. 1984; 159(1):21-40. PMC: 2187195. DOI: 10.1084/jem.159.1.21. View

Klein G, Sjogren H, Klein E, Hellstrom K . Demonstration of resistance against methylcholanthrene-induced sarcomas in the primary autochthonous host. Cancer Res. 1960; 20:1561-72. View

Festenstein H, Alonzo A, FERLUGA J, Ma B, Santamaria M, Marelli O . Further molecular and functional evidence for the expression of H-2 allodeterminants on the AKR leukemia, K36. Transplant Proc. 1983; 15(4):2107-10. View

Burnet F . A certain symmetry: histocompatibility antigens compared with immunocyte receptors. Nature. 1970; 226(5241):123-6. DOI: 10.1038/226123a0. View

Embleton M, HEIDELBERGER C . Antigenicity of clones of mouse prostate cells transformed in vitro. Int J Cancer. 1972; 9(1):8-18. DOI: 10.1002/ijc.2910090103. View

Basombrio M, Prehn R . Studies on the basis for diversity and time of appearance of antigens in chemically induced tumors. Natl Cancer Inst Monogr. 1972; 35:117-24. View

Invernizzi G, Parmiani G . Tumour-associated transplantation antigens of chemically induced sarcomata cross reacting with allogeneic histocompatibility antigens. Nature. 1975; 254(5502):713-4. DOI: 10.1038/254713a0. View

Murphy D, Okumura K, Herzenberg L, McDevitt H . A new I subregion (I-J) marked by a locus (Ia-4) controlling surface determinants on suppressor T lymphocytes. J Exp Med. 1976; 144(3):699-712. PMC: 2190409. DOI: 10.1084/jem.144.3.699. View

10.

Nowell P . The clonal evolution of tumor cell populations. Science. 1976; 194(4260):23-8. DOI: 10.1126/science.959840. View

11.

Ames B . Identifying environmental chemicals causing mutations and cancer. Science. 1979; 204(4393):587-93. DOI: 10.1126/science.373122. View

12.

Leibson P, Loken M, Panem S, Schreiber H . Clonal evolution of myeloma cells leads to quantitative changes in immunoglobulin secretion and surface antigen expression. Proc Natl Acad Sci U S A. 1979; 76(6):2937-41. PMC: 383725. DOI: 10.1073/pnas.76.6.2937. View

13.

Womack J . Single gene differences controlling enzyme properties in the mouse. Genetics. 1979; 92(1 Pt 1 Suppl):s5-12. View

14.

DeLuca D, Kripke M, Marchalonis J . Induction and specificity of antisera from mice immunized with syngeneic UV-induced tumors. J Immunol. 1979; 123(6):2696-703. View

15.

Glasebrook A, Fitch F . Alloreactive cloned T cell lines. I. Interactions between cloned amplifier and cytolytic T cell lines. J Exp Med. 1980; 151(4):876-95. PMC: 2185823. DOI: 10.1084/jem.151.4.876. View

16.

Flood P, Kripke M, Rowley D, Schreiber H . Suppression of tumor rejection by autologous anti-idiotypic immunity. Proc Natl Acad Sci U S A. 1980; 77(4):2209-13. PMC: 348682. DOI: 10.1073/pnas.77.4.2209. View

17.

Lemke H, Hammerling G, Hammerling U . Fine specificity analysis with monoclonal antibodies of antigens controlled by the major histocompatibility complex and by the Qa/TL region in mice. Immunol Rev. 1979; 47:175-206. DOI: 10.1111/j.1600-065x.1979.tb00293.x. View

18.

Pravtcheva D, DeLeo A, Ruddle F, Old L . Chromosome assignment of the tumor-specific antigen of a 3-methylcholanthrene-induced mouse sarcoma. J Exp Med. 1981; 154(3):964-77. PMC: 2186453. DOI: 10.1084/jem.154.3.964. View

19.

Kripke M . Immunologic mechanisms in UV radiation carcinogenesis. Adv Cancer Res. 1981; 34:69-106. DOI: 10.1016/s0065-230x(08)60239-0. View

20.

Steinmetz M, Moore K, Frelinger J, Sher B, Shen F, Boyse E . A pseudogene homologous to mouse transplantation antigens: transplantation antigens are encoded by eight exons that correlate with protein domains. Cell. 1981; 25(3):683-92. DOI: 10.1016/0092-8674(81)90175-6. View