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 Cell-mediated lympholysis of N-(3-nitro-4-hydroxy-5-iodophenylacetyl)-beta-anaylglycylglycyl-modified autologous lymphocytes. Effector cell specificity to modified cell surface components controlled by the H-2K and H-2D serological regions of the murine major histocompatibility complex.

1976 ◽  
Vol 143 (1) ◽  
pp. 127-142 ◽  
Author(s):  
T G Rehn ◽  
G M Shearer ◽  
H S Koren ◽  
J K Inman
Keyword(s):  
Major Histocompatibility Complex ◽  
Cell Surface ◽  
Effector Cell ◽  
Antigenic Determinants ◽  
Target Cells ◽  
Major Histocompatibility ◽  
Effector Cells ◽  
Modifying Agent ◽  
Histocompatibility Complex ◽  
Cell Specificity

Splenic lymphocytes from four C57BL/10 congenic mouse strains were sensitized in vitro to N(-3-nitro-4-hydroxy-5-iodophenylacetyl)-beta-alanylglycylglycyl-(N) modified autologous lymphocytes. The effector cells generated after 5 days of culture were assayed on a series of either N-modified phytohemagglutinin-stimulated spleen cells or N-modified tumor cells. The results indicated in all cases that both N modification of the targets and H-2 homology between the modified stimulating and target cells are required for lysis to occur. In each case the effector cells were found to lyse N-modified target cells only when there was homology at either or both ends of the major histocompatibility complex (MHC) between the stimulator and target cells. B10.BR lysed targets sharing alleles at K (or K plus I-A) and/or at D. B10.A effector cell specificity was mapped to K (or K plus I-A) and/or the D half of the MHC (D or D plus I-C and/or S). The two regions of specificity determined for B10.D2 effector cells were D (or D plus S plus I-C) and a region not including D of the MHC. C57BL/10 effector cells lysed N-modified targets only if there was target cell H-2 homology at K, I-A, and I-B or at the D serological region. As in the trinitrophenyl (TNP) system (6) B10.BR and B10.A effector cells lysed targets sharing K end H-2 serological regions greater than target cells sharing D-end serological regions. The C57BL/10 effector cells were shown to react to the K end greater than the D end, which differed from the equal reactivity seen in the TNP system for this strain. The data are consistent with the hypothesis that the antigen recognized by the effector cell includes an altered H-2 serological cell surface product. That the reaction is not "hapten specific" and the H-2 homology is required only for effector:target cell interaction was excluded by the use of two F1 combinations in which lysis of only N-modified target cells sharing the H-2 haplotype with the stimulating parental strain was obtained. Finally, it was demonstrated that N and TNP modification create distinct new antigenic determinants, since an effector cell sensitized to one modifying agent will lyse only H-2 matched target modified with that same modifying agent.

scholarly journals Primary in vitro cell-mediated lympholysis reaction of NZB mice against unmodified targets syngeneic at the major histocompatibility complex.

1978 ◽  
Vol 147 (5) ◽  
pp. 1435-1448 ◽  
Author(s):  
U Botzenhardt ◽  
J Klein ◽  
M Ziff
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Cell System ◽  
Cytotoxic T Cell ◽  
Mouse Strains ◽  
Major Histocompatibility ◽  
Effector Cells ◽  
Histocompatibility Complex ◽  
2D Strain

T-cell cytotoxicity of NZV mice was tested after in vitro sensitization against a group of H-2 identical strains (BALB/c, B10.D2, DBA/2, HW19). A highly significant and unexpected unidirectional cell-mediated lympholysis (CML) reaction by the sensitized NZB effector cells on these targets was found. After sensitization in vitro with stimulator cells of one H-2d strain, NZB effector cells (H-2d) lysed all other H-2d targets and to a lesser degree, some non-H-2d targets (C57BL/10, DBA/1, B10.Q, CBA, B10.S, A.SW). NZB targets were not lysed. Differences in the major histocompatibility region between NZB and other H-2d strains could be excluded as a possible explanation for the observed reaction of NZB (H-2d) against other H-2d strains. These results consequently represent the first description of a primary in vitro CML directed against determinants not coded for in the major histocompatibility complex. The responsible effector cells are demonstrated to be T cells. The CML of NZB against H-2 identiical targets appears best explained by a reaction against minor histocompatibility antigens. This, and the observed cross-reactions, would indicate that the cytotoxic T-cell system in NZB mice is not subjected to restrictions found in all normal mouse strains tested until now under similar conditions. It is suggested that this hyperreactivity is related to the autoimmune responsiveness of the NZB strain.

scholarly journals T cell determinant structure: cores and determinant envelopes in three mouse major histocompatibility complex haplotypes.

1991 ◽  
Vol 173 (3) ◽  
pp. 609-617 ◽  
Author(s):  
G Gammon ◽  
H M Geysen ◽  
R J Apple ◽  
E Pickett ◽  
M Palmer ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
T Cell Response ◽  
Single Amino Acid ◽  
Foreign Protein ◽  
Antigenic Determinants ◽  
Mouse Strains ◽  
Major Histocompatibility ◽  
Mouse Major Histocompatibility Complex ◽  
Histocompatibility Complex

T lymphocytes recognize discrete regions on an antigen. The specificity of the T cell responses in three mouse strains of differing major histocompatibility complex (MHC) haplotype to a protein antigen, lysozyme, was analyzed using a series of peptides that walk the antigen in single amino acid steps. These peptide series were synthesized using the pin synthesis system, which was modified to allow the peptides to be cleaved from the pins into a physiological buffer free of toxic compounds. This methodology overcomes many of the problems associated with the production of peptides for screening proteins for antigenic determinants. The T cell determinants for the three strains were markedly different. This result points out the limitations of algorithms predicting determinants without reference to the MHC, and the importance of the empirical methodology. This analysis of the T cell response to lysozyme constitutes the most complete study of reactivity to a foreign protein to date and illustrates many important features of antigen recognition by T cells, e.g., presence of major and minor determinant regions. The outer boundaries of each immunogenic region, the determinant envelope, are difficult to define from recently immunized lymph nodes because of the heterogeneity in T cell recognition. However, core sequences common to all the immunogenic peptides in a continuous sequence can be easily defined.

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 Selective turnover and shedding of H-2K and H-2D antigens is controlled by the major histocompatibility complex. Implications for H-2-restricted recognition.

1980 ◽  
Vol 152 (4) ◽  
pp. 783-795 ◽  
Author(s):  
S G Emerson ◽  
D B Murphy ◽  
R E Cone
Keyword(s):  
Major Histocompatibility Complex ◽  
Cell Surface ◽  
In Vitro Culture ◽  
Residence Times ◽  
Major Histocompatibility ◽  
Spleen Cells ◽  
Chemically Modified ◽  
Histocompatibility Complex ◽  
Murine Spleen

Lactoperoxidase-catalyzed cell surface radioiodination and incorporation of [3H]-leucine were employed to radiolabel H-2K and H-2D antigens of murine spleen cells. The fate of H-2 antigens was monitored by in vitro culture of labeled cells and isolation of labeled antigens from detergent lysates of the cells and culture supernates obtained at different times during culture. H-2Kk antigens were found to be rapidly turned over and shed by CBA/J cells, whereas the turnover of H-2Dk antigens was extremely slow. Analysis of the membrane residence times of surface-labeled H-2K and H-2D antigens on spleen cells from various H-2-congenic and -recombinant strains demonstrated variations in the shedding rates of H-2K and H-2D antigens, which were controlled by genes mapping in the major histocompatibility complex. These variations show a striking correlation with published, genetically controlled quantitative variations in the cytotoxic response of T lymphocytes to chemically modified or virus-infected syngeneic cells.

scholarly journals Monoclonal rat anti-major histocompatibility complex antibodies display specificity for rat, mouse, and human target cells.

1980 ◽  
Vol 151 (5) ◽  
pp. 1139-1150 ◽  
Author(s):  
D E Smilek ◽  
H C Boyd ◽  
D B Wilson ◽  
C M Zmijewski ◽  
F W Fitch ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Cross Reactivity ◽  
Lymphoid Cells ◽  
Brown Norway ◽  
Mouse Strains ◽  
Target Cells ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Antibody Specificities ◽  
High Degree

24 monoclonal rat antibodies are described that are reactive with determinants encoded by the major histocompatibility complex (MHC) of the rat. These hybridoma antibodies were derived by fusing mutant mouse myeloma cells to spleen cells from Lewis rats immunized with allogeneic Brown Norway cells. All 24 antibodies are cytotoxic for both Brown Norway target cells and target cells from the appropriate MHC congenic rats. Pattern of cytotoxicity and hemagglutination strongly suggest reactivity against class I (K or D equivalent) rat MHC determinants. Cytotoxic cross-reactivity patterns were generated for each monoclonal antibody on a panel of rat and mouse lymphoid cells and human peripheral T lymphocytes. A high degree of interspecies cross-reactivity was noted with approximately one-half of the antibodies positive on human and/or mouse target cells. 11 antibodies recognized polymorphic determinants in the mouse, and, by using target cells from MHC congenic mouse strains, it was shown that these determinants are encoded by genes within the H-2 complex. Finally, by considering the overall reactivity patterns of these monclonal antibodies on all target cells, one can show that these 24 antibodies represent a minimum of 14 antibody specificities.

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 A MOUSE B-CELL ALLOANTIGEN DETERMINED BY GENE(S) LINKED TO THE MAJOR HISTOCOMPATIBILITY COMPLEX

1973 ◽  
Vol 138 (6) ◽  
pp. 1289-1304 ◽  
Author(s):  
David H. Sachs ◽  
James L. Cone
Keyword(s):  
Major Histocompatibility Complex ◽  
Lymph Node ◽  
T Cell ◽  
B Cells ◽  
Cell Surface ◽  
B Cell ◽  
Surface Antigen ◽  
Major Histocompatibility ◽  
Spleen Cells ◽  
Histocompatibility Complex

Antibodies cytotoxic for only a subpopulation of C57Bl/10 lymph node and spleen cells were detected when rat antiserum against B10.D2 was exhaustively absorbed with B10.A lymphocytes. Antibodies of similar specificity were also detected in B10.A anti-B10.D2 and in B10.A anti-C57Bl/10 alloantisera. Reactions with recombinant strains of mice indicate that the cell-surface antigen(s) responsible for this specificity is determined by gene(s) in or to the left of the Ir-1 region of the major histocompatibility complex. A variety of criteria implicate B cells as the subpopulation of lymphocytes bearing this antigen. In view of these data and the recent report by others of a T-cell alloantigen determined by gene(s) in the major histocompatibility complex, it seems possible that there may be a variety of H-2-linked alloantigens expressed preferentially on subclasses of lymphocytes.

Sign in / Sign up

Export Citation Format

Share Document