Abstract

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)

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA024433-09
Application #
3166438
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1978-05-01
Project End
1989-06-30
Budget Start
1987-07-01
Budget End
1989-06-30
Support Year
9
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of California Santa Barbara
Department
Type
Schools of Arts and Sciences
DUNS #
City
Santa Barbara
State
CA
Country
United States
Zip Code
93106

  Publications

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