CCR5 Is Required for Regulation of Alloreactive T-Cell Responses to Single Class II MHC-Mismatched Murine Cardiac Grafts

Previous data from many groups show that both class I and class II-restricted T cells recognize short synthetic peptides in the context of their respective MHC molecules (9-18), all of the peptides described to date are restricted to only a single class of MHC molecules; however, structural homology between the class I and II MHC molecules and the use of similar TCRs by class I and II-restricted T cells suggest that antigen recognition mechanisms are similar in both systems. To directly compare antigen recognition in the two systems, we analyzed peptides for the ability to function in both a class I and II-restricted system and found that seven of seven individual peptides tested stimulate both class I and II-restricted T cell responses. In addition, two of the peptides can function in different species stimulating both human class I and murine class II T cell responses. Thus, the process of T cell recognition of antigen in the context of MHC molecules was highly conserved in evolution not only between the class I and class II MHC systems, but also between the murine and human species.

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Design of Glycopeptides Used to Investigate Class II MHC Binding and T-Cell Responses Associated with Autoimmune Arthritis

PLoS ONE ◽

10.1371/journal.pone.0017881 ◽

2011 ◽

Vol 6 (3) ◽

pp. e17881 ◽

Cited By ~ 14

Author(s):

Ida E. Andersson ◽

C. David Andersson ◽

Tsvetelina Batsalova ◽

Balik Dzhambazov ◽

Rikard Holmdahl ◽

...

Keyword(s):

T Cell ◽

T Cell Responses ◽

Class Ii ◽

Autoimmune Arthritis ◽

Cell Responses ◽

Class Ii Mhc

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Functional Heterogeneity of Human T Cell Responses to Class I and Class II MHC Antigens

Histocompatibility Testing 1984 ◽

10.1007/978-3-642-69770-8_233 ◽

1984 ◽

pp. 622-623

Author(s):

N. E. Goeken ◽

M. K. Eckerle ◽

P. J. Lioubin ◽

T. S. Staggs

Keyword(s):

T Cell ◽

T Cell Responses ◽

Class Ii ◽

Class I ◽

Functional Heterogeneity ◽

Mhc Antigens ◽

Cell Responses ◽

Human T Cell ◽

Class Ii Mhc ◽

Class Ii Mhc Antigens

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HIV Controllers Exhibit Enhanced Frequencies of Major Histocompatibility Complex Class II Tetramer+ Gag-Specific CD4+ T Cells in Chronic Clade C HIV-1 Infection

Journal of Virology ◽

10.1128/jvi.02477-16 ◽

2017 ◽

Vol 91 (7) ◽

Cited By ~ 10

Author(s):

Faatima Laher ◽

Srinika Ranasinghe ◽

Filippos Porichis ◽

Nikoshia Mewalal ◽

Karyn Pretorius ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Mhc Class Ii ◽

T Cell Responses ◽

Class Ii ◽

Single Class ◽

Cell Responses ◽

Clade C ◽

Hiv Controllers ◽

Hiv 1

ABSTRACT Immune control of viral infections is heavily dependent on helper CD4+ T cell function. However, the understanding of the contribution of HIV-specific CD4+ T cell responses to immune protection against HIV-1, particularly in clade C infection, remains incomplete. Recently, major histocompatibility complex (MHC) class II tetramers have emerged as a powerful tool for interrogating antigen-specific CD4+ T cells without relying on effector functions. Here, we defined the MHC class II alleles for immunodominant Gag CD4+ T cell epitopes in clade C virus infection, constructed MHC class II tetramers, and then used these to define the magnitude, function, and relation to the viral load of HIV-specific CD4+ T cell responses in a cohort of untreated HIV clade C-infected persons. We observed significantly higher frequencies of MHC class II tetramer-positive CD4+ T cells in HIV controllers than progressors (P = 0.0001), and these expanded Gag-specific CD4+ T cells in HIV controllers showed higher levels of expression of the cytolytic proteins granzymes A and B. Importantly, targeting of the immunodominant Gag41 peptide in the context of HLA class II DRB1*1101 was associated with HIV control (r = −0.5, P = 0.02). These data identify an association between HIV-specific CD4+ T cell targeting of immunodominant Gag epitopes and immune control, particularly the contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infection. Furthermore, these results highlight the advantage of the use of class II tetramers in evaluating HIV-specific CD4+ T cell responses in natural infections. IMPORTANCE Increasing evidence suggests that virus-specific CD4+ T cells contribute to the immune-mediated control of clade B HIV-1 infection, yet there remains a relative paucity of data regarding the role of HIV-specific CD4+ T cells in shaping adaptive immune responses in individuals infected with clade C, which is responsible for the majority of HIV infections worldwide. Understanding the contribution of HIV-specific CD4+ T cell responses in clade C infection is particularly important for developing vaccines that would be efficacious in sub-Saharan Africa, where clade C infection is dominant. Here, we employed MHC class II tetramers designed to immunodominant Gag epitopes and used them to characterize CD4+ T cell responses in HIV-1 clade C infection. Our results demonstrate an association between the frequency of HIV-specific CD4+ T cell responses targeting an immunodominant DRB1*11-Gag41 complex and HIV control, highlighting the important contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infections.

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Primary stimulation by dendritic cells induces antiviral proliferative and cytotoxic T cell responses in vitro.

Journal of Experimental Medicine ◽

10.1084/jem.169.4.1255 ◽

1989 ◽

Vol 169 (4) ◽

pp. 1255-1264 ◽

Cited By ~ 175

Author(s):

S E Macatonia ◽

P M Taylor ◽

S C Knight ◽

B A Askonas

Keyword(s):

T Cells ◽

Dendritic Cells ◽

T Cell ◽

T Cell Responses ◽

Class Ii ◽

Cytotoxic T Cell ◽

Hanging Drop ◽

Cell Responses ◽

Class Ii Mhc

We used well-gassed hanging drop (20 microliters) cultures with high concentrations of purified T cells from normal BALB/c mice to examine whether dendritic cells (DC) can induce primary antiviral proliferative T cell responses and generate virus-specific CTL. We found that DC exposed to infectious influenza virus in vitro or in vivo in small numbers (0.1-1%) resulted in strong proliferation of responder T cells within 3 d, and this was strongly inhibited by antibodies to class II MHC molecules. In addition, in 5-d cultures, the influenza-treated DC generated CTL specifically able to lyse influenza-infected syngeneic target cells bearing MHC class I antigens. The most potent nucleoprotein (NP) epitope recognized by BALB/c CTL is peptide 147-158 (Arg156-) and influenza-infected DC in vitro stimulated CTL recognizing this peptide, thus mimicking the response in mice primed by intranasal influenza infection. We also induced T cell proliferation and virus-specific CTL in cultures of normal T cells by stimulating with DC pulsed with the natural NP sequence 147-158 or the potent peptide 147-158 (Arg156-). Small numbers of peritoneal exudate cells, after activation with Con A to produce class II MHC expression and after removal of DC with a specific mAb (33DI), did not lead to primary CTL generation but initiated secondary stimulation in vitro. Our results using the hanging drop culture method and DC as APC have implications for studying the T cell repertoire for viral components in humans without the necessity of previous immunization.

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Encapsulation of Cryptococcus neoformans with Glucuronoxylomannan Inhibits the Antigen-Presenting Capacity of Monocytes

Infection and Immunity ◽

10.1128/iai.66.2.664-669.1998 ◽

1998 ◽

Vol 66 (2) ◽

pp. 664-669 ◽

Cited By ~ 58

Author(s):

Cinzia Retini ◽

Anna Vecchiarelli ◽

Claudia Monari ◽

Francesco Bistoni ◽

Thomas R. Kozel

Keyword(s):

T Cells ◽

T Cell ◽

Cryptococcus Neoformans ◽

T Cell Responses ◽

Class Ii ◽

Mhc Molecules ◽

Cell Responses ◽

Class Ii Mhc ◽

Antigen Presenting ◽

Cells Cultured

ABSTRACT This report examines the effect of the major capsular polysaccharide of Cryptococcus neoformans, glucuronoxylomannan (GXM), on the antigen-presenting capability of human monocytes treated with acapsular cells of C. neoformans. We found that pretreatment of acapsular cryptococci with GXM downregulates, in a dose-dependent manner, the antigen-presenting capacity of monocytes, leading to reduced proliferative T-lymphocyte responses. Similar levels of suppression occurred when monocytes were exposed to encapsulated cryptococci or acapsular cryptococci that were pretreated with GXM. The magnitude of the T-cell response correlated with the ability of monocytes to ingest the yeast. Supernatant fluids from cocultures of monocytes and T cells cultured with encapsulated cryptococci contained higher levels of interleukin-10 (IL-10) than supernatant fluids of cells with acapsular cryptococci. Addition of anti-IL-10 monoclonal antibodies to the incubation medium of monocytes and T cells cultured with encapsulated cryptococci restored proliferative T-cell responses to levels observed during culture with acapsular cryptococci. Finally, treatment of monocytes with encapsulated cryptococci or GXM-treated acapsular cryptococci suppressed expression of class II major histocompatibility complex (MHC) molecules in a manner consistent with previous reports of IL-10-mediated suppression of class II MHC molecules and suppression of proliferative T-cell responses. These results suggest a link between GXM encapsulation, increased IL-10 synthesis by monocytes, decreased expression of class II MHC molecules on monocytes, and reduced proliferative T-cell responses.

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