Antigen Processing: Current Issues, Exceptional Cases (Thy 1 Alloantigen, MHC Class-II-Restricted Cytolytic T Cells), and Implications for Vaccine Development

Author(s):  
Benjamin M. Chain ◽  
N. Avrion Mitchison ◽  
Timothy J. Mitchison ◽  
D. Huw Davies ◽  
Janusz Marcinkiewicz
1996 ◽  
Vol 183 (3) ◽  
pp. 1083-1092 ◽  
Author(s):  
R Wen ◽  
G A Cole ◽  
S Surman ◽  
M A Blackman ◽  
D L Woodland

Recent studies have shown that only a subset of major histocompatibility complex (MHC) class II molecules are able to present bacterial superantigens to T cells, leading to the suggestion that class-II associated peptides may influence superantigen presentation. Here, we have assessed the potential role of peptides on superantigen presentation by (a) analyzing the ability of superantigens to block peptide-specific T cell responses and (b) analyzing the ability of individual peptides to promote superantigen presentation on I-Ab-expressing T2 cells that have a quantitative defect in antigen processing. A series of peptides is described that specifically promote either toxic shock syndrome toxin (TSST) 1 or staphylococcal enterotoxin A (SEA) presentation. Whereas some peptides promoted the presentation of TSST-1 (almost 5,000-fold in the case of one peptide), other peptides promoted the presentation of SEA. These data demonstrate that MHC class II-associated peptides differentially influence the presentation of bacterial superantigens to T cells.


1989 ◽  
Vol 2 ◽  
pp. 45-53 ◽  
Author(s):  
Benjamin M. Chain ◽  
N.Avrion Mitchison ◽  
Timothy J. Mitchison ◽  
D.Huw Davies ◽  
Janusz Marcinkiewicz

Blood ◽  
1996 ◽  
Vol 88 (9) ◽  
pp. 3508-3512 ◽  
Author(s):  
K Garrigan ◽  
P Moroni-Rawson ◽  
C McMurray ◽  
I Hermans ◽  
N Abernethy ◽  
...  

We have compared dendritic cells (DC) isolated from mouse spleen, or generated in vitro from bone marrow (BM) precursors cultured in granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4), for the ability to process and present soluble antigen and stimulate major histocompatibility complex (MHC) Class II-restricted T cells. DC from spleen or BM cultures were equally able to stimulate the in vitro proliferation of allogeneic T cells or of antigen-specific T-cell receptor (TCR)-transgenic T cells. Both DC populations also induced comparable levels of IL-2 secretion by a T-cell hybridoma. Therefore, splenic and BM-derived DC express comparable levels of (Antigen + MHC Class II) ligands and/or costimulatory molecules and have comparable ability to stimulate T-cell responses. When presentation of a native protein antigen, rather than peptide, was evaluated, BM-derived DC were at least 50 times better than splenic DC at stimulating the proliferation of TCR-transgenic T cells. The antigen processing ability of the two populations was similar only when splenic DC were used immediately ex vivo. Therefore, unlike spleen DC, BM-derived DC maintain the capacity to process protein antigen for MHC Class II presentation during in vitro culture. Due to these characteristics, BM-derived DC may represent a useful tool in immunotherapy studies, as they combine high T-cell stimulatory properties with the capacity to process and present native antigen.


2018 ◽  
Vol 215 (10) ◽  
pp. 2617-2635 ◽  
Author(s):  
Yoshinaga Ito ◽  
Orr Ashenberg ◽  
Jason Pyrdol ◽  
Adrienne M. Luoma ◽  
Orit Rozenblatt-Rosen ◽  
...  

A number of autoimmunity-associated MHC class II proteins interact only weakly with the invariant chain–derived class II–associated invariant chain peptide (CLIP). CLIP dissociates rapidly from I-Ag7 even in the absence of DM, and this property is related to the type 1 diabetes–associated β57 polymorphism. We generated knock-in non-obese diabetic (NOD) mice with a single amino acid change in the CLIP segment of the invariant chain in order to moderately slow CLIP dissociation from I-Ag7. These knock-in mice had a significantly reduced incidence of spontaneous type 1 diabetes and diminished islet infiltration by CD4 T cells, in particular T cells specific for fusion peptides generated by covalent linkage of proteolytic fragments within β cell secretory granules. Rapid CLIP dissociation enhanced the presentation of such extracellular peptides, thus bypassing the conventional MHC class II antigen-processing pathway. Autoimmunity-associated MHC class II polymorphisms therefore not only modify binding of self-peptides, but also alter the biochemistry of peptide acquisition.


2013 ◽  
Vol 2 (4) ◽  
pp. 341-350 ◽  
Author(s):  
Junko Matsuzaki ◽  
Takemasa Tsuji ◽  
Immanuel Luescher ◽  
Lloyd J. Old ◽  
Protul Shrikant ◽  
...  

Blood ◽  
2003 ◽  
Vol 101 (11) ◽  
pp. 4472-4478 ◽  
Author(s):  
Sarah Flynn ◽  
Brigitta Stockinger

Abstract This paper addresses the capacity of naive, effector, and memory CD4 T cells to control growth of a major histocompatibility complex (MHC) class II—positive B-cell lymphoma in vivo. To assess the role of T cells on their own without contributions by B cells, antibodies, or natural killer (NK) cells, we generated pure effector or memory CD4 T cells in Rag–/–gc–/– mice deficient in endogenous lymphocytes and NK cells. Lymphoma cells expressing a model antigen were injected into mice with T cells of cognate specificity that were either naive or in effector or resting memory state. Naive T cells were unable to prevent tumor growth, probably due to delay of efficient cross-presentation by dendritic cells. However, both effector and memory T cells, dependent on the amount of antigen available, controlled the tumor for a considerable period of time without the need for dendritic cell stimulation. Nevertheless, the tumor eventually grew uncontrolled in all cases. This was not because of a defect in T-cell homing to the tumor site or loss of MHC class II or costimulatory molecules by the tumor, but reflected mutual paralysis of T-cell responsiveness and antigen processing by tumor cells.


2020 ◽  
Vol 8 (3) ◽  
pp. 144-156
Author(s):  
Şule KARATAŞ ◽  
Fatma SAVRAN OĞUZ

Introduction: Peptides obtained by processing intracellular and extracellular antigens are presented to T cells to stimulate the immune response. This presentation is made by peptide receptors called major histocompatibility complex (MHC) molecules. The regulation mechanisms of MHC molecules, which have similar roles in the immune response, especially at the gene level, have significant differences according to their class. Objective: Class I and class II MHC molecules encoded by MHC genes on the short arm of the sixth chromosome are peptide receptors that stimulate T cell response. These peptides, which will enable the recognition of the antigen from which they originate, are loaded into MHC molecules and presented to T cells. Although the principles of loading and delivering peptides are similar for both molecules, the peptide sources and peptide loading mechanisms are different. In addition, class I molecules are expressed in all nucleated cells while class II molecules are expressed only in Antigen Presentation Cells (APC). These differences; It shows that MHC class I is not expressed by exactly the same transcriptional mechanisms as MHC class II. In our article, we aimed to compare the gene expressions of both classes and reveal their similarities and differences. Discussion and Conclusion: A better understanding of the transcriptional mechanisms of MHC molecules will reveal the role of these molecules in diseases more clearly. In our review, we discussed MHC gene regulation mechanisms with presence of existing informations, which is specific to the MHC class, for contribute to future research. Keywords: MHC class I, MHC class II, MHC gene regulation, promoter, SXY module, transcription


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