scholarly journals T cell receptor genes in a series of class I major histocompatibility complex-restricted cytotoxic T lymphocyte clones specific for a Plasmodium berghei nonapeptide: implications for T cell allelic exclusion and antigen-specific repertoire.

1991 ◽  
Vol 174 (6) ◽  
pp. 1371-1383 ◽  
Author(s):  
J L Casanova ◽  
P Romero ◽  
C Widmann ◽  
P Kourilsky ◽  
J L Maryanski
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
T Lymphocyte ◽  
Plasmodium Berghei ◽  
Cytotoxic T Lymphocyte ◽  
Class I ◽  
Allelic Exclusion ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Histocompatibility Complex

We report here the first extensive study of a T cell repertoire for a class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocyte (CTL) response. We have found that the T cell receptors (TCRs) carried by 28 H-2Kd-restricted CTL clones specific for a single Plasmodium berghei circumsporozoite nonapeptide are highly diverse in terms of V alpha, J alpha, and J beta segments and aminoacid composition of the junctional regions. However, despite this extensive diversity, a high proportion of the TCRs contain the same V beta segment. These results are in contrast to most previously reported T cell responses towards class II MHC-peptide complexes, where the TCR repertoires appeared to be much more limited. In our study, the finding of a dominant V beta in the midst of otherwise highly diverse TCRs suggests the importance of the V beta segment in shaping the T cell repertoire specific for a given MHC-peptide complex. As an additional finding, we observed that nearly all clones have rearranged both TCR alpha loci. Moreover, as many as one-third of the CTL clones that we analyzed apparently display two productive alpha rearrangements. This argues against a regulated model of sequential recombination at the alpha locus and consequently raises the question of whether allelic exclusion of the TCR alpha chain is achieved at all.

scholarly journals Indirect allorecognition of platelets by T helper cells during platelet transfusions correlates with anti-major histocompatibility complex antibody and cytotoxic T lymphocyte formation [published erratum appears in Blood 1995 Dec 15;86(12):4710]

Blood ◽  
1995 ◽  
Vol 86 (2) ◽  
pp. 805-812 ◽  
Author(s):  
JW Semple ◽  
ER Speck ◽  
YP Milev ◽  
V Blanchette ◽  
J Freedman
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Mhc Class I ◽  
T Lymphocyte ◽  
Nk Cell ◽  
Cytotoxic T Lymphocyte ◽  
Spleen Cells ◽  
Histocompatibility Complex ◽  
Platelet Transfusions

To study the cellular immunology of platelet-induced alloimmunization, a murine transfusion model was developed. BALB/c (H-2d) recipient mice were transfused weekly with 2 x 10(8) platelets or 10(3) leukocytes from C57BL/6 (H-2b) donor mice. Recipient antidonor major histocompatibility complex (MHC) class I alloantibodies could be detected in flow cytometric assays by the fifth platelet transfusion. In contrast, when leukocytes only were transfused, alloantibodies were not detected. In vitro assays demonstrated that murine H-2b platelets were positive for MHC class I expression but lacked MHC class II molecules on their membranes and were unable to stimulate proliferation or cytokine production when incubated with naive H-2d spleen cells. In vivo, however, platelet transfusions induced two distinct patterns of cell-mediated reactivity. First, during the initial transfusions and before alloantibody formation, there was induction of T-cell anergy, characterized by the inability of recipient T cells to respond to Concanavalin A (ConA) or to proliferate in an antidonor mixed lymphocyte reaction (MLR), together with suppressed natural killer (NK) cell activity. This unresponsiveness was associated with a transient increase in nitric oxide (NO)-dependent cytotoxicity and interleukin-1 (IL-1) production. Second, once alloantibodies developed, significantly increased antidonor CD8+ cytotoxic T lymphocyte (CTL) and NK cell responses were observed. At this time, when recipient spleen cells were depleted of CD8+ T cells and incubated with only donor platelets in 7- day antigen-presenting cell (APC) assays, enhanced proliferation and IL- 2 production occurred. These cellular responses were not seen when 10(3) allogeneic leukocytes were transfused. Thus, the results suggest that leukoreduced platelet transfusions induce antidonor MHC antibodies and CD8+ CTL responses in recipient mice. At the same time, the transfusions induced recipient CD4+ T-cell activation when incubated with donor platelets in the presence of syngeneic APCs, an indirect recognition pathway that correlates with the time of alloantibody production.

Carrier-reactive hapten-specific cytotoxic T lymphocyte clones originate from a highly preselected T cell repertoire: implications for chemical-induced self-reactivity

1995 ◽  
Vol 25 (10) ◽  
pp. 2788-2796 ◽  
Author(s):  
Stefan Martin ◽  
Helga Ruh ◽  
Sabine Hebbelmann ◽  
Ulrike Pflugfelder ◽  
Barbara Rüde ◽  
...  
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
T Cell Repertoire ◽  
Cell Repertoire

scholarly journals Escape in One of Two Cytotoxic T-Lymphocyte Epitopes Bound by a High-Frequency Major Histocompatibility Complex Class I Molecule, Mamu-A*02: a Paradigm for Virus Evolution and Persistence?

2002 ◽  
Vol 76 (22) ◽  
pp. 11623-11636 ◽  
Author(s):  
Thorsten U. Vogel ◽  
Thomas C. Friedrich ◽  
David H. O'Connor ◽  
William Rehrauer ◽  
Elizabeth J. Dodds ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Class I ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecule ◽  
Immunodeficiency Virus ◽  
Ctl Responses

ABSTRACT It is now accepted that an effective vaccine against AIDS must include effective cytotoxic-T-lymphocyte (CTL) responses. The simian immunodeficiency virus (SIV)-infected rhesus macaque is the best available animal model for AIDS, but analysis of macaque CTL responses has hitherto focused mainly on epitopes bound by a single major histocompatibility complex (MHC) class I molecule, Mamu-A*01. The availability of Mamu-A*01-positive macaques for vaccine studies is therefore severely limited. Furthermore, it is becoming clear that different CTL responses are able to control immunodeficiency virus replication with varying success, making it a priority to identify and analyze CTL responses restricted by common MHC class I molecules other than Mamu-A*01. Here we describe two novel epitopes derived from SIV, one from Gag (Gag71-79 GY9), and one from the Nef protein (Nef159-167 YY9). Both epitopes are bound by the common macaque MHC class I molecule, Mamu-A*02. The sequences of these two eptiopes are consistent with the molecule's peptide-binding motif, which we have defined by elution of natural ligands from Mamu-A*02. Strikingly, we found evidence for the selection of escape variant viruses by CTL specific for Nef159-167 YY9 in 6 of 6 Mamu-A*02-positive animals. In contrast, viral sequences encoding the Gag71-79 GY9 epitope remained intact in each animal. This situation is reminiscent of Mamu-A*01-restricted CTL that recognize Tat28-35 SL8, which reproducibly selects for escape variants during acute infection, and Gag181-189 CM9, which does not. Differential selection by CTL may therefore be a paradigm of immunodeficiency virus infection.

scholarly journals Highly Restricted T Cell Repertoire Shaped by a Single Major Histocompatibility Complex–Peptide Ligand in the Presence of a Single Rearranged T Cell Receptor β Chain

1998 ◽  
Vol 188 (5) ◽  
pp. 897-907 ◽  
Author(s):  
Yoshinori Fukui ◽  
Osamu Hashimoto ◽  
Ayumi Inayoshi ◽  
Takahiro Gyotoku ◽  
Tetsuro Sano ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Positive Selection ◽  
Peptide Ligand ◽  
T Cell Repertoire ◽  
Major Histocompatibility ◽  
Cell Repertoire ◽  
Histocompatibility Complex ◽  
Self Peptides ◽  
Selection Of

The T cell repertoire is shaped by positive and negative selection of thymocytes through the interaction of α/β-T cell receptors (TCR) with self-peptides bound to self-major histocompatibility complex (MHC) molecules. However, the involvement of specific TCR-peptide contacts in positive selection remains unclear. By fixing TCR-β chains with a single rearranged TCR-β irrelevant to the selecting ligand, we show here that T cells selected to mature on a single MHC–peptide complex express highly restricted TCR-α chains in terms of Vα usage and amino acid residue of their CDR3 loops, whereas such restriction was not observed with those selected by the same MHC with diverse sets of self-peptides including this peptide. Thus, we visualized the TCR structure required to survive positive selection directed by this single ligand. Our findings provide definitive evidence that specific recognition of self-peptides by TCR could be involved in positive selection of thymocytes.

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