Monoclonal antibodies (MAb) have been used to probe the relationship of cytolytic T lymphocyte (CTL) surface molecules to CTL function. Rat MAb to mouse CTL were generated. Twelve MAb so obtained gave preferential binding to T cells as compared to B cells, and three of these recognized previously undescribed surface polypeptides. These Mab and more broadly reactive and previously obtained MAb were tested for their ability to block CTL-mediated killing in the absence of complement. To ensure that any observed blocking was due to binding of MAb to the effector cell rather than the target cell, a xenogeneic mouse CTL anti-rat BN lymphoma target cell system was utilized (MAb and target cells both of rat origin). Of 24 MAb tested here, 21 had little or no effect on CTL function, including those to H-2, Thy-1, Lyt-1, Ly 5, Ly 6, Lgp 100, and at least six other defined antigens. We confirmed inhibition of killing with two MAb to Lyt-2,3. Another MAb, M7/14, gave profound and consistent blockade of CTL function. It was confirmed that M7/14 MAb blocks killing by binding to the mouse CTL and does not bind to the rat lymphoma target cells used for the CTL assay. The findings suggest that the antigen defined by M7/14, termed a lymphocyte function-associated antigen, LFA-1, participates in or is closely associated with the mechanism of CTL-mediated killing. LFA-1 contains two polypeptide chains of 180,000 and 95,000 Mr and is distinct from other described lymphocyte glycoproteins. LFA-1 thus represents both a previously undescribed lymphocyte surface antigen and molecular site for blockade of CTL-mediated killing.
Publications
Lymphocyte function-associated antigen 1 (LFA-1): A surface antigen distinct from Lyt-2,3 that participates in T lymphocyte-mediated killing. Proc Natl Acad Sci USA 78, 7, 4535-4539 (1981).Abstract
Quantitation of light chain synthesis in myeloma x spleen cell hybrids and identification of myeloma chain loss variants using radioimmunoassay. J. Immunol. Methods 37, 2, 139-152 (1980).Abstract
Cell-surface differentiation in the mouse. Characterization of "jumping" and "lineage" antigens using xenogeneic rat monoclonal antibodies. Monoclonal antibodies 185-217 (1980).
Monoclonal antibodies and cell surface antigens. Genetics and human biology: possibilities and realities. Ciba Foundation Symp. No. 66 3, 1-16 (1979).
Mac-1: a macrophage differentiation antigen identified by monoclonal antibody. Eur. J. Immunol. 9, 4, 301-306 (1979).
Monoclonal xenogeneic antibodies to mouse leukocyte antigens: Identification of macrophage-specific and other differentiation antigens. Curr. Topics Microbiol. Immunol. 81, 45-50 (1978).
Monoclonal xenogeneic antibodies to murine cell surface antigens: identification of novel leukocyte differentiation antigens. Eur. J. Immunol. 8, 8, 539-551 (1978).Abstract
Studies of the structure of the human Ia-like antigen. Ir genes and Ia antigens 229-234 (1978).
Chemical and immunological characterization of HLA-linked B-lymphocyte alloantigens. Cold Spring Harbor Symp. Quant. Biol. 41, 387-395 (1977).
Structure of HLA-A and HLA-B antigens isolated from cultured human lymphocytes. Cold Spring Harbor Symp. Quant. Biol. 41, 323-329 (1977).Abstract
Detergent solubilization, purification, and separation of specificities of HLA antigens from a cultured human lymphoblastoid line, RPMI 4265. J. Biol. Chem. 252, 13, 4682-4693 (1977).Abstract
Subunit and disulfide structure of monomeric and dimeric forms of detergent-soluble HLA antigens. J. Biol. Chem. 252, 4694-4700 (1977).Abstract
Purification and structural characterisation of human HLA-linked B-cell antigens. Nature 268, 5617, 213-218 (1977).Abstract
Isolation and structure of products of the human histocompatibility gene complex. Role of histocompatibility gene complex in immune responses. Proc. Int. Conf. at Brook Lodge, Mich. 35, 621-643 (1976).
The immunoglobulin-like structure of human histocompatibility antigens. Federation Proceedings 35, 1177-1182 (1976).
Detergent-soluble HLA antigens contain a hydrophilic region at the COOH-terminus and a penultimate hydrophobic region. Proc. Natl. Acad. Sci. U. S. A. 73, 2481-2485 (1976).Abstract
The structure of products of the major histocompatibility complex in man. 27. Mosbach Colloquium: The immune system 202-219 (1976).