While the possible involvement of beta?2?-microglobulin in cytotoxic T lymphocytes (CTL) recognition events is still under investigation, with no conclusive results emerging from this study yet, concrete progress made in several other areas includes: (1) the dml mutant is shown to express a hybrid H-2D?d?/H-2L?d? protein that is probably the product of fused genes; (2) CTL responses to cell surface-coupled proteins can now be studied since we developed a way of covalently conjugating a million or more protein molecules to cells that then remain viable and stable for over a day in culture and that serve as excellent targets for lysis by antibody plus complement and ADCC; (3) we discovered that some monoclonal antibodies are excellent ADCC mediators and that ADCC efficiency depends both on the subclass (IgG2a or IgG3) and the orientation of the antibody on the cell; (4) normal human lymphocytes are not good ADCC targets; (5) human K effectors induce rapid fragmentation of the nuclear DNA in mouse target cells; and (6) nuclear DNA fragmentation is induced in mouse target cells only and not in human target cells when such targets are lysed by ADCC, CTL, or NK cells. (CS)

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National Cancer Institute (NCI)
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Allergy and Immunology Study Section (ALY)
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University of California Santa Barbara
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Song, E S; Young, K; Sears, D W (1990) Rat and human natural killers exhibit contrasting immunoglobulin G subclass specificities in antibody-dependent cellular cytotoxicity reflecting differences in their Fc receptors (Fc gamma R). J Leukoc Biol 48:524-30
Zeger, D L; Osman, N; Hennings, M et al. (1990) Mouse macrophage beta subunit (CD11b) cDNA for the CR3 complement receptor/Mac-1 antigen. Immunogenetics 31:191-7
Sears, D W; Osman, N; Tate, B et al. (1990) Molecular cloning and expression of the mouse high affinity Fc receptor for IgG. J Immunol 144:371-8
Parker, S E; Sears, D W (1990) H-2 restriction and serotype crossreactivity of anti-reovirus cytotoxic T lymphocytes (CTL). Viral Immunol 3:77-87
Parker, S E; Sun, Y H; Sears, D W (1988) Differential expression of the ASGM1 antigen on anti-reovirus and alloreactive cytotoxic T lymphocytes (CTL). J Immunogenet 15:215-26
Christiaansen, J E; Burnside, S S; Sears, D W (1987) Apparent sensitivity of human K lymphocytes to the spatial orientation and organization of target cell-bound antibodies as measured by the efficiency of antibody-dependent cellular cytotoxicity (ADCC). J Immunol 138:2236-43
Hunt, P; Burnside, S S; Sears, D W (1985) Evidence of only one H-2D/L-related glycoprotein in H-2dm1 mutant cells. J Immunogenet 12:33-44
Ozato, K; Takahashi, H; Appella, E et al. (1985) Polymorphism of murine major histocompatibility Class I antigen: assignment of putative allodeterminants to distinct positions of the amino acid sequence within the first external domain of the antigen. J Immunol 134:1749-58
Christiaansen, J E; Sears, D W (1985) Lack of lymphocyte-induced DNA fragmentation in human targets during lysis represents a species-specific difference between human and murine cells. Proc Natl Acad Sci U S A 82:4482-5
Sears, D W; Christiaansen, J E (1985) Mechanism of rapid tumor lysis by human ADCC: mediation by monoclonal antibodies and fragmentation of target cell DNA. Adv Exp Med Biol 184:509-25