Control of Cytotoxic T-Lymphocyte Responses By Class-I and Class-II H-2 Molecules, Studied with H-2 Mutants

Ir Genes ◽  
1983 ◽  
pp. 377-381
Author(s):  
Cornelis J. Melief ◽  
Leo P. de Waal ◽  
Marijke J. Stukart ◽  
W. Martin Kast ◽  
Roger W. Melvold
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Class Ii ◽  
Class I ◽  
Lymphocyte Responses

Shaping the Repertoire of Cytotoxic T-Lymphocyte Responses: Explanation for the Immunodominance Effect Whereby Cytotoxic T Lymphocytes Specific for Immunodominant Antigens Prevent Recognition of Nondominant Antigens

Blood ◽  
1999 ◽  
Vol 93 (3) ◽  
pp. 952-962 ◽  
Author(s):  
Stéphane Pion ◽  
Gregory J. Christianson ◽  
Pierre Fontaine ◽  
Derry C. Roopenian ◽  
Claude Perreault
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Cell Receptor ◽  
Rapid Expansion ◽  
Class I ◽  
Tcr Signals ◽  
Lymphocyte Responses ◽  
Antigen Presenting ◽  
Dominant Epitope

The immunodominance effect, whereby the presence of immunodominant epitopes prevents recognition of nondominant determinants presented on the same antigen-presenting cell (APC) considerably restricts the repertoire of cytotoxic T lymphocyte (CTL) responses. To elucidate the molecular basis of the immunodominance effect, we compared the interactions of a dominant (B6dom1) and a nondominant epitope (H-Y) with their restricting class I molecule (H2-Db), and their ability to trigger cognate CTLs. We found that B6dom1/Db complexes behaved as optimal T-cell receptor (TCR) ligands and triggered a more rapid in vivo expansion of cognate CTLs than H-Y/Db complexes. The superiority of the dominant epitope was explained by its high cell surface density (1,012 copies/cell for B6dom1v 10 copies/cell for H-Y) and its optimal affinity for cognate TCRs. Based on these results, we conclude that dominant class I–associated epitopes are those that have optimal ability to trigger TCR signals in CTLs. We propose that the rapid expansion of CTLs specific for dominant antigens should enable them to compete more successfully than other CTLs for occupancy of the APC surface.

Tumor-Specific Cytotoxic T Lymphocyte Responses against Chondrosarcoma with HLA Haplotype Loss Restricted by the Remaining HLA Class I Allele

2001 ◽  
Vol 286 (4) ◽  
pp. 786-791 ◽  
Author(s):  
Akio Hiraki ◽  
Kazuma Ikeda ◽  
Tadashi Yoshino ◽  
Toshihiko Kaneshige ◽  
Katsuyuki Kiura ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Hla Class I ◽  
Class I ◽  
Lymphocyte Responses

scholarly journals Use of “one-pot, mix-and-read” peptide-MHC class I tetramers and predictive algorithms to improve detection of cytotoxic T lymphocyte responses in cattle

2014 ◽  
Vol 45 (1) ◽  
pp. 50 ◽  
Author(s):  
Nicholas Svitek ◽  
Andreas Hansen ◽  
Lucilla Steinaa ◽  
Rosemary Saya ◽  
Elias Awino ◽  
...  
Keyword(s):  
Mhc Class I ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Class I ◽  
One Pot ◽  
Predictive Algorithms ◽  
Lymphocyte Responses

scholarly journals Cytotoxic T lymphocyte nonresponsiveness to the male antigen H-Y in the H-2Db mutants bm13 and bm14. Complementation of the response in F1 crosses with the I-Ab mutant bm12 nonresponder and failure of B6 or Db mutant mice tolerant of each other to respond to allogeneic male cells.

1983 ◽  
Vol 158 (5) ◽  
pp. 1537-1546 ◽  
Author(s):  
L P De Waal ◽  
R W Melvold ◽  
C J Melief
Keyword(s):  
T Cell ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Class Ii ◽  
T Helper Cell ◽  
Class I ◽  
F1 Hybrids ◽  
T Helper ◽  
Cell Repertoire ◽  
Ctl Response

The cytotoxic T-lymphocyte (CTL) response against the male-specific antigen H-Y in C57BL/6 (B6, H-2b) mice is regulated by the I-Ab and Db molecules. From previous studies, we concluded that the bm12 I-Ab mutant does not respond to H-Y, because of a deletion in its T-helper-cell repertoire. We now demonstrate that two Db mutants, bm13 and bm14, also fail to generate a CTL response to H-Y. The bm12 class-II mutant on one hand and the bm13 and bm14 class-I mutants on the other complemented each other for the H-Y-specific CTL response in (bm12 X bm13)F1 and (bm 12 X bm 14)F1 hybrids. This indicates that the need for tolerance of the mutant class II and class I molecules in these hybrids does not create deletions in the I-Ab-restricted T helper cell and Db-restricted CTL repertoire for H-Y. This study constitutes the first demonstration with H-2 mutants that a CTL response controlled by class I and class II MHC molecules is complemented in an F1 cross between a class I and a class II nonresponder. (B6 X bm 13)F1 and (B6 X bm 14)F1 hybrids only responded to H-Y when the antigen was presented on F1 or B6 antigen-presenting cells (apc) but not on Db mutant apc. B6 or Db mutant responders rendered neonatally tolerant of each other failed to respond to the H-Y antigen presented on the tolerogenic allogeneic cell. In the tolerized animals, a response was only seen with responder (B6) type T cells and responder type (B6) apc, indicating that both the T cell source and the MHC type of the apc have to be taken into account in this system. Thus, Ir genes may act at the level of both the T cell repertoire and antigen presentation.

scholarly journals Polymorphisms in HLA Class I Genes Associated with both Favorable Prognosis of Human Immunodeficiency Virus (HIV) Type 1 Infection and Positive Cytotoxic T-Lymphocyte Responses to ALVAC-HIV Recombinant Canarypox Vaccines

2001 ◽  
Vol 75 (18) ◽  
pp. 8681-8689 ◽  
Author(s):  
Richard A. Kaslow ◽  
Charles Rivers ◽  
Jianming Tang ◽  
Thomas J. Bender ◽  
Paul A. Goepfert ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Natural Infection ◽  
Class I ◽  
Favorable Prognosis ◽  
Immunodeficiency Virus ◽  
Lymphocyte Responses ◽  
Hiv 1

ABSTRACT Carriers of certain human leukocyte antigen class I alleles show favorable prognosis of human immunodeficiency virus type 1 (HIV-1) infection, presumably due to effective CD8+ cytotoxic T-lymphocyte responses, but close relationships between class I variants mediating such responses to natural and to vaccine HIV-1 antigen have not been established. During 6 to 30 months of administration and follow-up in trials of ALVAC-HIV recombinant canarypox vaccines, cells from 42% of 291 HIV-1-negative vaccinated subjects typed at class I loci responded to an HIV-1 protein in a lytic bulk CD8+ cytotoxic T-lymphocyte assay. By 2 weeks after the second dose, higher proportions of vaccinees carrying one of two alleles consistently associated with slower progression of natural HIV-1 infection reacted at least once: B∗27 carriers reacted to Gag (64%; odds ratio [OR] = 10.3, P = 0.001) and Env (36%; OR = 4.6, P = 0.04), and B∗57 carriers reacted to Env (44%; OR = 6.6, P < 0.05). By 2 weeks after the third or fourth dose, B∗27 carriers had responded (two or more reactions) to Gag (33%; OR = 4.4, P< 0.05) and B∗57 carriers had responded to both Gag (39%; OR = 5.3, P = 0.013) and Env (39%; OR = 9.5,P = 0.002). Homozygosity at class I loci, although conferring an unfavorable prognosis following natural infection, showed no such disadvantage for vaccine response. Individual class I alleles have not previously demonstrated such clear and consistent relationship with both the clinical course of an infection and cellular immunity to a vaccine against the infectious agent. This proof of principle that class I an alleles modulate both processes has implications for development of HIV-1 and presumably other vaccines.

scholarly journals Cytotoxic T-Lymphocyte Precursor Frequencies in BALB/c Mice after Acute Respiratory Syncytial Virus (RSV) Infection or Immunization with a Formalin-Inactivated RSV Vaccine

1998 ◽  
Vol 72 (11) ◽  
pp. 8971-8975 ◽  
Author(s):  
Ralph A. Tripp ◽  
Larry J. Anderson
Keyword(s):  
Respiratory Syncytial Virus ◽  
Mhc Class I ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Class Ii ◽  
Class I ◽  
Rsv Infection ◽  
Potential Vaccine ◽  
Syncytial Virus ◽  
Spleen Lymphocytes

ABSTRACT A better understanding of the immune response to live and formalin-inactivated respiratory syncytial virus (RSV) is important for developing nonlive vaccines. In this study, major histocompatibility complex (MHC) class I- and II-restricted, RSV-specific cytotoxic T-lymphocyte precursor (CTLp) frequencies were determined in bronchoalveolar lavage (BAL) samples and spleen lymphocytes of BALB/c mice intranasally infected with live RSV or intramuscularly inoculated with formalin-inactivated RSV (FI-RSV). After RSV infection, both class I- and class II-restricted CTLps were detected by day 4 or 5 postinfection (p.i.). Peak CTLp frequencies were detected by day 7 p.i. The class II-restricted CTLp frequencies in the BAL following RSV infection were less than class I-restricted CTLp frequencies through day 14 p.i., during which class I-restricted CTLp frequencies remained elevated, but then declined by 48 days p.i. The frequencies of class II-restricted CTLps in the BAL were 2- to 10-fold less than those of class I-restricted CTLps. For spleen cells, frequencies of both MHC class I- and II-restricted CTLps to live RSV were similar. In contrast, class II-restricted CTLps predominated in FI-RSV-vaccinated mice. RSV challenge of vaccinated mice resulted in an increase in the frequency of class I-restricted CTLps at day 3 p.i. but did not enhance class II-restricted CTLp frequencies. These studies demonstrate differences in the CTLp response to live RSV infection compared with FI-RSV immunization and help define possible mechanisms of enhanced disease after FI-RSV immunization. In addition, these studies provide a quantitative means to address potential vaccine candidates by examining both MHC class I- and II-restricted CTLp frequencies.

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