scholarly journals Generation of primary cytotoxic lymphocytes against non-major histocompatibility complex antigens by anti-Ia serum plus complement-treated lymphocytes.

1980 ◽  
Vol 151 (5) ◽  
pp. 1305-1310 ◽  
Author(s):  
C E Hayes ◽  
S Macphail ◽  
F H Bach
Keyword(s):  
Major Histocompatibility Complex ◽  
Suppressor Cell ◽  
Target Cells ◽  
Cytotoxic Lymphocytes ◽  
Major Histocompatibility ◽  
Cytotoxic Cells ◽  
Major Histocompatibility Complex Antigens ◽  
Cytotoxic Response ◽  
Histocompatibility Complex

The results presented in this paper demonstrate that responding cells that remain after anti-Ia serum plus complement (C) treatment generate a highly significant in vitro cytotoxic response against minor histocompatibility complex antigens. The cytotoxic response appears to be antigen specific in that target cells of strains other than the sensitizing strain are not lysed, or lysed to a lesser extent. The cytotoxic cells are susceptible to anti-Thy-1 plus C lysis. Anti-Ia serum may function by removing an unprimed suppressor cell, although other mechanisms cannot be ruled out.

scholarly journals The control of specificity of cytotoxic T lymphocytes by the major histocompatibility complex (AG-B) in rats and identification of a new alloantigen system showing no AG-B restriction.

1977 ◽  
Vol 146 (6) ◽  
pp. 1773-1790 ◽  
Author(s):  
A Marshak ◽  
P C Doherty ◽  
D B Wilson
Keyword(s):  
Major Histocompatibility Complex ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Third Party ◽  
Cytotoxic T Cell ◽  
Target Cells ◽  
Cytotoxic Lymphocytes ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Ct Antigens

The regulatory influence of the rat major histocompatibility complex (MHC) (Ag-B complex) on the specificity of cytotoxic T lymphocytes was investigated. It was shown that the effector cells were specific for the original Ag-B phenotype in rat systems in which the responder and stimulator cell populations were unquestionably MHC identical but expressed different minor alloantigens of viral antigens. However, combined in vivo immunization and restimulation in culture of lymphocytes from rat strains previously thought to be MHC compatible resulted in the generation of cytotoxic T lymphocytes which effectively lyse not only target cells from the specific stimulating strains but also, to varying degrees, target cells from third party strains regardless of their Ag-B haplotypes. Genetic analysis indicates that expression of these cytotoxic T-cell-defined ("CT") antigens, found on both T and B lymphocytes, detectable thus far only with cytotoxic lymphocytes, is controlled by a single locus which segregates in backcross populations with the rat MHC. Discrepancies between the nature of CT antigens of the rat Ag-B and I-region specificities of the mouse H-2 are discussed.

scholarly journals Cell-mediated lympholysis of trinitrophenyl-modified autologous lymphocytes. Effector cell specificity to modified cell surface components controlled by H-2K and H-2D serological regions of the murine major histocompatibility complex.

1975 ◽  
Vol 141 (6) ◽  
pp. 1348-1364 ◽  
Author(s):  
G M Shearer ◽  
T G Rehn ◽  
C A Garbarino
Keyword(s):  
Major Histocompatibility Complex ◽  
Cell Surface ◽  
Antigenic Determinants ◽  
Mouse Strains ◽  
Target Cells ◽  
Major Histocompatibility ◽  
Resistant Mouse ◽  
Effector Cells ◽  
Histocompatibility Complex

Splenic lymphocytes from four C57BL/10 congenic resistant mouse strains were sensitized in vitro with trinitrophenyl (TNP)-modified autologous spleen cellsmthe effector cells generated were incubated with 51-Cr-labeled unmodified or TNP-modified spleen or tumor target cells, and the percentage of specific lympholysis determined. The results obtained using syngeneic-, congenic-, recombinante, and allogeneic-modified target cells indicated that TNP modification of the target cells was a necessary but insufficient requirement for lympholysis. Intra-H-2 homology either between modified stimulating cells and modified target cells or between responding lymphocytes and modified target cells was also important in the specificity for lysis. Homology at the K serological region or at K plus I-A in the B10.A and B10BR strains, and at either the D serological region or at some other region (possibly K) in the B10.D2 and C57BL/10 strains were shown to be necessary in order to detect lympholysis. Experiments using (B10itimes C57BL/10)F1 responding lymphocytes sensitized and assayed with TNP-modified parental cells indicated that the homology required for lympholysis was between modified stimulating and modified target cellsmthe possibility is raised that histocompatibility antigens may serve in the autologous system as cell surface components which are modified by viruses or autoimmune complexes to form cell-bound modified-self antigens, which are particularly suited for cell-mediated immune reactions. Evidence is presented suggesting that H-2-linked Ir genes are expressed in the TNP-modified autologous cytotoxic system. These findings imply that the major histocompatibility complex can be functionally involved both in the response potential to and in the formation of new antigenic determinants involving modified-self components.

scholarly journals The major histocompatibility complex determines susceptibility to cytotoxic T cells directed against minor histocompatibility antigens.

1975 ◽  
Vol 142 (6) ◽  
pp. 1349-1364 ◽  
Author(s):  
M J Bevan
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Cytotoxic T Cells ◽  
Target Cells ◽  
Major Histocompatibility ◽  
Effector Cells ◽  
Minor Histocompatibility Antigens ◽  
Cytotoxic Cells ◽  
Histocompatibility Complex ◽  
Self Recognition

Cytotoxic cells were generated by immunizing one strain of mouse with cells from an allogeneic strain which carries the same H-2 region. The effector cells assayed in a 4 h 51Cr release assay were shown to be T cells and indistinguishable, except in specificity, from cytotoxic T cells directed at H-2 alloantigens. Although the genetic differences between responder and stimulator cells responsible for the immunization did not code in H-2, the H-2 complex did restrict susceptibility of target cells. For example, BALB.B cytotoxic cells (H-2b) immunized against and capable of lysing C57BL/6 cells (H-2b) would not lyse B6.C/H-2d target cells. C57BL/6 and B6.C/H-2d are congenic and differ in the H-2 region. Two hypotheses are considered to explain the H-2 restriction of susceptibility to cytotoxic T cells generated by an H-2 identical alloimmunization. (a) The dual (self) recognition hypothesis states that the cytotoxic cell has two recognition units, one for H-2-coded structures and another clonally restricted receptor for the minor alloantigen. (b) The interaction antigen hypothesis states that all the surface alloantigenic determinants recognized by cytotoxic T cells are the result of interaction between H-2- and non-H-2-coded gene products. Two lines of evidence, one with F1 effector cells and the other a cold target competition experiment, are presented which argue strongly in favor of the interaction antigen hypothesis. The regions of H-2 required to be histocompatible were mapped to the D region and to the left of IC, probably the K region. These results, and recent work on the response to virus-infected and TNP-modified syngeneic cells, suggest that cytotoxic cells are restricted in specificity to preferentially recognizing alterations in structures that are coded in the major histocompatibility complex.

scholarly journals Concanavalin A-mediated activation of antigen-primed lymphocytes into secondary cytotoxic lymphocytes.

1977 ◽  
Vol 145 (2) ◽  
pp. 293-301 ◽  
Author(s):  
B Bonavida
Keyword(s):  
Major Histocompatibility Complex ◽  
Cytotoxic Activity ◽  
Concanavalin A ◽  
Specific Inhibitor ◽  
Target Cells ◽  
Cytotoxic Lymphocytes ◽  
Con A ◽  
Cytotoxic Cells ◽  
Histocompatibility Complex

A secondary specific cytotoxic response is obtained when lymphocytes primed in vivo to a tumor allograft are exposed to Con A in culture. The secondary cytotoxic cells generated are specific to target cells bearing antigens of the primary sensitizing cells and are qualitatively indistinguishable from the response obtained upon secondary antigenic stimulation. The cell-mediated cytotoxicity is independent of concanavalin A (Con A) and is not affected by the Con A-specific inhibitor, alpha-methyl-D-mannose pyranoside. Furthermore, cultures containing a mixture of submitogenic concentrations of Con A and stimulating antigens showed synergy and augmentation of cytotoxic activity. It is suggested that activation of prekiller cells by Con A into CTL may be mediated via the same or similar receptors normally triggered by the stimulating antigens. Functional similarities between ConA and the lymphocyte-defined antigens of the major histocompatibility complex region are discussed.

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