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 T cell receptor interaction with peptide/major histocompatibility complex (MHC) and superantigen/MHC ligands is dominated by antigen.

1993 ◽  
Vol 178 (2) ◽  
pp. 713-722 ◽  
Author(s):  
E W Ehrich ◽  
B Devaux ◽  
E P Rock ◽  
J L Jorgensen ◽  
M M Davis ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Amino Acid ◽  
T Cell ◽  
T Cell Activation ◽  
Single Amino Acid ◽  
Receptor Interaction ◽  
Antigenic Peptides ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

While recent evidence strongly suggests that the third complementarity determining regions (CDR3s) of T cell receptors (TCRs) directly contact antigenic peptides bound to major histocompatibility complex (MHC) molecules, the nature of other TCR contact(s) is less clear. Here we probe the extent to which different antigens can affect this interaction by comparing the responses of T cells bearing structurally related TCRs to cytochrome c peptides and staphylococcal enterotoxin A (SEA) presented by 13 mutant antigen-presenting cell (APC) lines. Each APC expresses a class II MHC molecule (I-Ek) with a single substitution of an amino acid residue predicted to be located on the MHC alpha helices and to point "up" towards the TCR. We find that very limited changes (even a single amino acid) in either a CDR3 loop of the TCR or in a contact residue of the antigenic peptide can have a profound effect on relatively distant TCR/MHC interactions. The extent of these effects can be as great as that observed between T cells bearing entirely different TCRs and recognizing different peptides. We also find that superantigen presentation entails a distinct mode of TCR/MHC interaction compared with peptide presentation. These data suggest that TCR/MHC contacts can be made in a variety of ways between the same TCR and MHC, with the final configuration apparently dominated by the antigen. These observations suggest a molecular basis for recent reports in which either peptide analogues or superantigens trigger distinct pathways of T cell activation.

scholarly journals Primary in vitro cytotoxic T cell response to non-major histocompatibility complex alloantigens in normal mice.

1982 ◽  
Vol 156 (2) ◽  
pp. 610-621 ◽  
Author(s):  
S Macphail ◽  
I Yron ◽  
O Stutman
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Calf Serum ◽  
Suppressor Cells ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Mouse Serum ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

We have shown for the first time that it is possible to consistently generate a primary in vitro cytotoxic T cell (Tc) response to non-major histocompatibility complex alloantigens using responder cells from a normal mouse strain. This was achieved by carrying out, in the generating phase, a limiting dilution procedure in which it appears that suppressor cells that inhibit Tc activation or expansion are too dilute to manifest their effect. Moreover, the response was observed in mouse serum-(MS) as well as fetal calf serum- (FCS) supplemented media, an important finding in the light of the anomalous nonspecific effects induced by FCS. The cytotoxic response produced in MS-supplemented media was shown to be highly specific in both the generating and effector phases, whereas the responses in FCS had a strong nonspecific component.

scholarly journals Major Histocompatibility Complex–independent Recognition of a Distinctive Pollen Antigen, Most Likely a Carbohydrate, by Human CD8+ α/β T Cells

1997 ◽  
Vol 186 (6) ◽  
pp. 899-908 ◽  
Author(s):  
Silvia Corinti ◽  
Raffaele De Palma ◽  
Angelo Fontana ◽  
Maria Cristina Gagliardi ◽  
Carlo Pini ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Cd8 T Cells ◽  
T Cell Response ◽  
Major Histocompatibility ◽  
T Cell Clones ◽  
Histocompatibility Complex ◽  
Cell Clones

We have isolated CD8+ α/β T cells from the blood of atopic and healthy individuals which recognize a nonpeptide antigen present in an allergenic extract from Parietaria judaica pollen. This antigen appears to be a carbohydrate because it is resistant to proteinase K and alkaline digestion, is hydrophilic, and is sensitive to trifluoromethane-sulphonic and periodic acids. In addition, on a reverse-phase high performance liquid chromatography column the antigen recognized by CD8+ T cells separates in a fraction which contains >80% hexoses (glucose and galactose) and undetectable amounts of proteins. Presentation of this putative carbohydrate antigen (PjCHOAg) to CD8+ T cell clones is dependent on live antigen presenting cells (APCs) pulsed for >1 h at 37°C, suggesting that the antigen has to be internalized and possibly processed. Indeed, fixed APCs or APCs pulsed at 15°C were both unable to induce T cell response. Remarkably, PjCHOAg presentation is independent of the expression of classical major histocompatibility complex (MHC) molecules or CD1. CD8+ T cells stimulated by PjCHOAg-pulsed APCs undergo a sustained [Ca2+]i increase and downregulate their T cell antigen receptors (TCRs) in an antigen dose– and time-dependent fashion, similar to T cells stimulated by conventional ligands. Analysis of TCR Vβ transcripts shows that six independent PjCHOAg-specific T cell clones carry the Vβ8 segment with a conserved motif in the CDR3 region, indicating a structural requirement for recognition of this antigen. Finally, after activation, the CD8+ clones from the atopic patient express CD40L and produce high levels of interleukins 4 and 5, suggesting that the clones may have undergone a Th2-like polarization in vivo. These results reveal a new class of antigens which triggers T cells in an MHC-independent way, and these antigens appear to be carbohydrates. We suggest that this type of antigen may play a role in the immune response in vivo.

scholarly journals T cell response specificity and magnitude against SIVmac239 are not concordant in major histocompatibility complex-matched animals

Retrovirology ◽  
2013 ◽  
Vol 10 (1) ◽  
pp. 116 ◽  
Author(s):  
Brian T Cain ◽  
Ngoc H Pham ◽  
Melisa L Budde ◽  
Justin M Greene ◽  
Jason T Weinfurter ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Cell Response ◽  
T Cell Response ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Response Specificity

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 Analysis of peptide binding patterns in different major histocompatibility complex/T cell receptor complexes using pigeon cytochrome c-specific T cell hybridomas. Evidence that a single peptide binds major histocompatibility complex in different conformations.

1989 ◽  
Vol 170 (5) ◽  
pp. 1609-1625 ◽  
Author(s):  
H Bhayani ◽  
Y Paterson
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Cytochrome C ◽  
Peptide Sequence ◽  
Single Amino Acid ◽  
Major Histocompatibility ◽  
Peptide Antigens ◽  
Receptor Complexes ◽  
Histocompatibility Complex ◽  
Single Peptide

The interaction of TCR, antigen, and MHC complex has been analyzed using synthetic peptide antigens and a series of single amino acid-substituted analogues. Two similar antigens, mouse cytochrome c (mcyt c) and pigeon cytochrome c (pcyt c), elicit T cell responses in strains of mice bearing MHC class II Ek beta Ek alpha (B10.A), Eb beta Ek alpha [B10.A(5R)], and Es beta Ek alpha [B10.S(9R)]. The immunogenic regions of these antigens are located in the peptide sequence p88-104 for pcyt c and m88-103 for mcyt c. The limited T cell repertoire for these antigens is comprised of four groups of T cell phenotypes that have very few differences in their TCR gene make up. In this paper, we examine the diversity in their fine specificity for each of the antigens, m88-103 and p88-104, complexed with each of the I-Ek haplotypes. Epitopes, i.e., residues that interact with the TCR, and agretopes, i.e., residues in the MHC-binding site, were assigned for the two peptide antigens in the presence of APC bearing E beta kEk alpha, Eb beta Ek alpha, or Eb beta Ek alpha using T cell hybridomas of the phenotypes I, IIIa, and IV. From our results, we conclude that first, the substitution of any residue between 95 and 104 of the cytochrome c peptide changed the antigenic potency of the peptide for at least one of the hybridomas. Second, each T cell type has a different recognition pattern of epitopes and agretopes for a particular antigen-MHC complex, thus, ruling out a static model of T cell recognition, which assigns certain, invariant agretopic residues to the peptide by which it interacts with the MHC molecule independently of the TCR. Third, the same T cell hybridoma responded to the antigens differently when presented on various MHC molecules, implying that overall changes in the MHC groove, as displayed by the three haplotypes, may affect the efficiency in binding the peptide. Fourth, since most of the residues are used as epitopes by at least one of the T cell specificities, the peptide appears to be recognized in a different conformation by each T cell hybridoma phenotype; and, finally, the epitopic and agretopic residues do not segregate, for any one of the T cell specificities, in such a way that suggests they are recognized in a helical conformation. In summary, our results suggest that a single peptide may generate diversity in the T cell response by virtue of its conformational flexibility within the TCR-MHC-antigen complex.

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 Major histocompatibility complex class II-expressing endothelial cells induce allospecific nonresponsiveness in naive T cells.

1996 ◽  
Vol 183 (4) ◽  
pp. 1603-1612 ◽  
Author(s):  
F M Marelli-Berg ◽  
R E Hargreaves ◽  
P Carmichael ◽  
A Dorling ◽  
G Lombardi ◽  
...  
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Major Histocompatibility Complex Class ◽  
Class Ii ◽  
T Cell Response ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

The role of endothelial cells (EC) in initiating a primary T cell response is of importance in clinical transplantation and autoimmunity since EC are the first allogeneic target encountered by the recipient's immune system and may display tissue-specific autoantigens in the context of an inflammatory response. In this study, we have investigated the antigen-presenting cell function of human umbilical vein-derived EC (HUVEC), depleted of constitutively major histocompatibility complex class II+ cells and induced to express class II molecules by interferon-gamma. The results show that HUVEC do not express B7 but can support proliferation by antigen-specific T cell clones. In contrast, they were unable to initiate a primary alloresponse using three independent HUVEC cultures and MHC class II-mismatched CD4+ T cells from eight donors. The response to HUVEC was reconstituted by trans-costimulation provided by DAP.3 transfectants expressing human B7.1. Coculture of peripheral blood T cells with EC expressing allogeneic DR molecules had markedly different effects on CD45RO+ and RA+ subsets. Subsequent reactivity of the RO+ T cells was unaffected by exposure to EC, indicating a neutral encounter. In contrast, culture with DR+ EC induced allospecific nonresponsiveness in RA+ T cells.

scholarly journals CD8+ T cell response to Mls-1a determinants involves major histocompatibility complex class II molecules.

1991 ◽  
Vol 173 (3) ◽  
pp. 779-782 ◽  
Author(s):  
Y Chvatchko ◽  
H R MacDonald
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Mhc Class Ii ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Class Ii ◽  
T Cell Response ◽  
Major Histocompatibility ◽  
Cell Responses ◽  
Histocompatibility Complex

Recent studies indicate that both CD4+ and CD8+ T lymphocytes proliferate in vitro in response to Mls-1a-encoded determinants. Using both immunogenetic and antibody blocking approaches we show here that Mls-1a responses of both subsets require expression of major histocompatibility complex (MHC) class II molecules (I-A and/or I-E) by the stimulator cells. Furthermore, CD8+ T cell responses to Mls-1a/class II MHC do not require (and are in fact inhibited by) the presence of functional CD8 molecules. Taken together, our data underscore the dramatic differences between CD8+ T cell responses to conventional peptide antigens as opposed to "superantigens" such as Mls-1a.

scholarly journals Delivery of a MalE CD4+-T-Cell Epitope into the Major Histocompatibility Complex Class II Antigen Presentation Pathway by Bordetella pertussis Adenylate Cyclase

2002 ◽  
Vol 70 (2) ◽  
pp. 1002-1005 ◽  
Author(s):  
Jir̆ina Loucká ◽  
Géraldine Schlecht ◽  
Jana Vodolánová ◽  
Claude Leclerc ◽  
Peter S̆ebo
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Adenylate Cyclase ◽  
Major Histocompatibility Complex Class ◽  
Class Ii ◽  
T Cell Response ◽  
Complex Class ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Presentation Pathway

ABSTRACT Recombinant adenylate cyclase toxoids are shown to deliver inserted foreign CD4+-T-cell epitopes into the major histocompatibility complex class II presentation pathway, inducing a specific CD4+-T-cell response in vivo and yielding in vitro stimulation of specific CD4+ T cells at a 100-times-higher molar efficiency than the free peptide containing the epitope.

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