scholarly journals Fine specificity of alloimmune cytotoxic T lymphocytes directed against H-2K. A study with Kb mutants.

1980 ◽  
Vol 151 (5) ◽  
pp. 993-1013 ◽  
Author(s):  
C J Melief ◽  
L P de Waal ◽  
M Y van der Meulen ◽  
R W Melvold ◽  
H I Kohn

The fine specificity of alloimmune cytotoxic T lymphocytes (CTL) was investigated in CTL responses across the smallest known H-2 differences, those based on mutation at a single H-2 locus. CTL were generated in all possible mixed lymphocyte culture (MLC) combinations among seven H-2Kb mutants and the mouse strain of origin, C57BL/6 (B6-H-2b). CTL were also generated in all F1 hybrid responder/homozygous stimulator-cell combinations among four Kb mutants and B6-H-2b. CTL activity was measured in cell-mediated lympholysis (CML) against target cells from all Kb mutants and B6-H-2b. Cross-reactivity against targets other than the MLC stimulator was extensive and led to the distinction of 64 CML target determinants. Two Kb mutants (B6-H-2bm6 and B6.C-H-2bm9) showed identical typing for all 64 CML determinants. CML reactions after MLC between these two haplotypes were mutually negative. The mutants B6-H-2bm3 and B6.C-H-2bm11 showed identical typing for 47 of the 64 determinants. Their close relationship is in agreement with the finding that H-2bm3 anti-H-2bm11 CTL were the only ones that exclusively lysed target cells of stimulator-cell genotype. On the basis of CML typing, the sequence of relatedness of the mutants with H-2b is as follows: bm6/bm9-bm10-bm3-bm1-bm11, bm6/bm9 being the closest to, and bm11 the most distant from H-2b. The extensive cross-reactivity of alloimmune CTL appears to reflect immunogenetic complexity rather than lack of specificity. Comparison with other reports supports the notion that the system of Kb CML determinants, recognized by alloimmune CTL, is at least partially overlapping with the H-2Kb specificity repertoire involved in the associative T cell recognition of virus-infected cells.

1975 ◽  
Vol 141 (4) ◽  
pp. 775-787 ◽  
Author(s):  
P F Piguet ◽  
H K Dewey ◽  
P Vassalli

Caryotypic analysis of the cells dividing in mouse parent-hybrid MLC showed an F1 hybrid cell proliferation, which varied depending upon the source of lymphoid cells used: strong in spleen MLC (sometimes equal to that of the parental cells), less marked in lymph node cell MLC, and most often absent in MLC between cortisone-resistant (CR) thymocytes. MLC between parental spleen cells and F1 CR thymocytes showed, however, that in certain conditions of culture F thymocytes can also proliferate. Using parental or F1 spleen cells lacking T lymphocytes, it was found that F1 cell proliferation is entirely dependent upon the presence of parental T cells, but does not require the presence of T lymphocytes among the F1 cells. Immunofluorescence analysis of the blasts observed in one-way MLC showed that about 70% of the parental blasts were T blasts, and 25%B blasts (containing a high proportion of plasmablasts); among the F1 blasts, there was also the same percentage of B blasts and plasmablasts, but many of the T blasts bore only small amounts of T-cell antigen (MTLA), and there was also about 20%of unstained blasts, possibly T blasts bearing MTLA in amounts undetectable by immunofluorescence. The possibility is discussed that the F1 responding T cells belong to a subpopulation performing a suppressive function; MLC lacking F1 T cells showed increased [3H] thymidine incorporation. The proliferation and differentiation of parental and F1 B cells may result mainly from an unspecific, "polyclonal" triggering.


1975 ◽  
Vol 142 (6) ◽  
pp. 1477-1487 ◽  
Author(s):  
H Wagner ◽  
D Götze ◽  
L Ptschelinzew ◽  
M Röllinghoff

Determinants controlled by the I region of the murine H-2 complex provoked the generation of cytotoxic T lymphocytes (CTL) in both a secondary and primary mixed lymphocyte culture. The stimulating determinants appeared to be controlled by loci within the I-A subregion. The target antigens of the CTL generated were present on both lipopolysaccharide- and concanavalin-induced blast lymphocytes, but were barely detectable on phytohemagglutinin-induced blast cells. The stimulating capacity for CTL induction of a complete H-2 complex incompatibility by far exceeded the sum of H-2D/K-region and I-region incompatibility, respectively.


1976 ◽  
Vol 143 (6) ◽  
pp. 1545-1550 ◽  
Author(s):  
O J Kuperman ◽  
F H Bach

The LD and SD antigens of the major histocompatibility complex subserve differential roles in the induction of the proliferative phase in mixed lymphocyte culture and in the cytotoxic reaction seen in cell-mediated lympholysis. The present study suggests that they also behave differently in the neonatal induction of tolerance. SD antigens appear to induce tolerance in the cytotoxic T lymphocytes very effectively, whereas LD antigens (or the cytotoxic targets coded by genes in the I and/or S regions) are relatively ineffective in this regard. LD antigens presented neonatally are effective at inducing tolerance in the proliferating helper cells.


1988 ◽  
Vol 89 (4) ◽  
pp. 561-573
Author(s):  
C. Foa ◽  
J.L. Mege ◽  
C. Capo ◽  
A.M. Benoliel ◽  
J.R. Galindo ◽  
...  

T-cell-mediated cytolysis is initiated by the formation of strong adhesions between killer and target cells. The present work was aimed at determining whether T lymphocytes might exert some mechanical stress on targets during the binding process. Target S194 myeloma cells were thus conjugated to cytotoxic T lymphocytes (CTLs) raised by mixed lymphocyte culture or a cloned lymphoid line that was no longer cytolytic (TG2OUA2). After incubation periods of various lengths, conjugates were processed for electron microscopy and micrographs were digitized for computerized analysis: the cell surface curvature (at the micrometre level) and rugosity (at the submicrometre level) were quantified in free and adhesion-involved regions. Also, the size of cell interaction areas and the distribution of intermembrane distances were measured. Finally, TG2OUA2 and target cells were aspirated into glass micropipettes with calibrated pressure in order to assay their resistance to deformation by mechanical forces. The following conclusions were suggested. (1) Formation of extensive contact zones (with a linear size of several micrometres) with tight intermembrane adhesion (more than 30% of the membrane contours in adhesive zones were separated by an apparent distance lower than 500 A) was essentially completed within less than one minute. (2) CTLs or TG2OUA2 cells were more villous than their targets, and they seemed to deform in adhesive zones in order to adapt to the target contour, rather than imposing some deformation on the target. This may be a general feature of actively adherent cells. (3) Some CTLs, but no TG2OUA2 cells, exhibited conspicuous protrusions extending towards the bound target. In this case, the target cell but not the CTL displayed markedly increased roughness in the adhesion area. (4) TG2OUA2 cells were more resistant to mechanical deformation than S194 target cells, in accordance with previous reports suggesting that the membrane of CTLs was more resistant than that of target tumour cells. Hence, CTLs might transiently impose mechanical stress on the target membrane during the course of lethal-hit delivery.


1978 ◽  
Vol 148 (6) ◽  
pp. 1458-1467 ◽  
Author(s):  
A McMichael

Cytotoxic T lymphocytes (CTL), specific for influenza A/X31 virus, were generated from human peripheral blood lymphocytes. These CTL lysed target cells that were infected with the same virus and that shared HLA A or B locus antigens. Minimal lysis was observed when HLA-D antigens were shared. Not all HLA A and B antigens were equally effective. Efficient lysis of target cells was seen when HLA A1, A3, B7, B8, B27 and BW21 were shared with the CTL, but when HLA A2 was the only shared antigen lysis was usually minimal. This deficiency in CTL function associated with HLA A2 was not absolute. It is suggested that the function of this antigen might be influenced by other surface molecules on the cell and in particular the other HLA products.


Nature ◽  
1981 ◽  
Vol 289 (5798) ◽  
pp. 559-563 ◽  
Author(s):  
Keiichiro Nakano ◽  
Ichiro Nakamura ◽  
Gustavo Cudkowicz

1999 ◽  
Vol 54 (2) ◽  
pp. 113-121 ◽  
Author(s):  
M.-A. Sol ◽  
N. Vacaresse ◽  
J. Lule ◽  
C. Davrinche ◽  
B. Gabriel ◽  
...  

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