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T cell recognition of non-peptidic antigens in infectious diseases.

Singhal A, Mori L, De Libero G - Indian J. Med. Res. (2013)

Bottom Line: Non-peptidic antigens do not bind to MHC molecules and are presented by other classes of antigen-presenting molecules.T cells specific for non-peptidic antigens have important roles in host defense against infections, autoimmunity, allergies and tumour immunosurveillance.Hence, understanding the molecular interactions between the antigen presenting cell (APC) and the T cells with non-peptidic specificity is of great relevance.

View Article: PubMed Central - PubMed

Affiliation: SIgN (Singapore Immunology Network), AFNx01STAR (Agency for Science, Technology & Research), Singapore; Experimental Immunology, Department of Biomedicine, University Hospital Basel, Basel, Switzerland, .

ABSTRACT
The immune system has evolved to recognize a wide range of antigenic molecules of self and non-self origin. The stimulatory antigens form complexes with antigen-presenting molecules and directly interact with the T cell receptor (TCR). Peptidic antigens associate with major histocompatibility complex (MHC) molecules and therefore, are indicated as MHC-restricted. Non-peptidic antigens do not bind to MHC molecules and are presented by other classes of antigen-presenting molecules. These non-MHC restricted antigens include glycolipid molecules, phosphorylated metabolites of the mevalonate pathway and vitamin B2 precursors. T cells specific for non-peptidic antigens have important roles in host defense against infections, autoimmunity, allergies and tumour immunosurveillance. Hence, understanding the molecular interactions between the antigen presenting cell (APC) and the T cells with non-peptidic specificity is of great relevance. Here, we review current knowledge of this type of T cells, their TCR repertoire, the structural aspects of recognized antigens, the mode of antigen recognition, and their function with special emphasis on their role in infectious diseases.

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Structure of 6,7-dimethyl-ribityllumazine (A) , 6-methyl-7-hydroxy-ribityllumazine (B) , and 6-hydroxymethyl-ribityllumazine (C).
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Figure 2: Structure of 6,7-dimethyl-ribityllumazine (A) , 6-methyl-7-hydroxy-ribityllumazine (B) , and 6-hydroxymethyl-ribityllumazine (C).

Mentions: MAIT cells react to APCs infected with a variety of microbes, including several Gram-negative and Gram-positive bacteria, Mycobacteria, Candida and Saccharomyces2111. Importantly, Streptococcus and Listeria species do not activate MAIT cells, indicating that the stimulatory antigen is conserved across many but not all microbial species. MAIT cells are also activated by fixed APCs co-cultured with Escherichia coli, suggesting that the antigen can be secreted by bacteria and may bind to MR1 on the surface of APC without internalization2. A recent study has shown that metabolic precursors of riboflavin, namely 6,7-dimethyl ribityllumazine, 6-methyl-7-OH-ribityllumazine, and 6-hydroxymethyl-ribityllumazine (Fig. 2) bind to MR1 and stimulate MAIT cells110. These metabolites are secreted by bacteria and a perfect correlation was found among the stimulatory bacterial species and their capacity to synthesize riboflavin. The size of these antigens is too small to fill the antigen-binding pocket of MR1, and, therefore, there is the possibility that other non-peptidic molecules may bind to MR1 and stimulate MR1-restricted T cells.


T cell recognition of non-peptidic antigens in infectious diseases.

Singhal A, Mori L, De Libero G - Indian J. Med. Res. (2013)

Structure of 6,7-dimethyl-ribityllumazine (A) , 6-methyl-7-hydroxy-ribityllumazine (B) , and 6-hydroxymethyl-ribityllumazine (C).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928695&req=5

Figure 2: Structure of 6,7-dimethyl-ribityllumazine (A) , 6-methyl-7-hydroxy-ribityllumazine (B) , and 6-hydroxymethyl-ribityllumazine (C).
Mentions: MAIT cells react to APCs infected with a variety of microbes, including several Gram-negative and Gram-positive bacteria, Mycobacteria, Candida and Saccharomyces2111. Importantly, Streptococcus and Listeria species do not activate MAIT cells, indicating that the stimulatory antigen is conserved across many but not all microbial species. MAIT cells are also activated by fixed APCs co-cultured with Escherichia coli, suggesting that the antigen can be secreted by bacteria and may bind to MR1 on the surface of APC without internalization2. A recent study has shown that metabolic precursors of riboflavin, namely 6,7-dimethyl ribityllumazine, 6-methyl-7-OH-ribityllumazine, and 6-hydroxymethyl-ribityllumazine (Fig. 2) bind to MR1 and stimulate MAIT cells110. These metabolites are secreted by bacteria and a perfect correlation was found among the stimulatory bacterial species and their capacity to synthesize riboflavin. The size of these antigens is too small to fill the antigen-binding pocket of MR1, and, therefore, there is the possibility that other non-peptidic molecules may bind to MR1 and stimulate MR1-restricted T cells.

Bottom Line: Non-peptidic antigens do not bind to MHC molecules and are presented by other classes of antigen-presenting molecules.T cells specific for non-peptidic antigens have important roles in host defense against infections, autoimmunity, allergies and tumour immunosurveillance.Hence, understanding the molecular interactions between the antigen presenting cell (APC) and the T cells with non-peptidic specificity is of great relevance.

View Article: PubMed Central - PubMed

Affiliation: SIgN (Singapore Immunology Network), AFNx01STAR (Agency for Science, Technology & Research), Singapore; Experimental Immunology, Department of Biomedicine, University Hospital Basel, Basel, Switzerland, .

ABSTRACT
The immune system has evolved to recognize a wide range of antigenic molecules of self and non-self origin. The stimulatory antigens form complexes with antigen-presenting molecules and directly interact with the T cell receptor (TCR). Peptidic antigens associate with major histocompatibility complex (MHC) molecules and therefore, are indicated as MHC-restricted. Non-peptidic antigens do not bind to MHC molecules and are presented by other classes of antigen-presenting molecules. These non-MHC restricted antigens include glycolipid molecules, phosphorylated metabolites of the mevalonate pathway and vitamin B2 precursors. T cells specific for non-peptidic antigens have important roles in host defense against infections, autoimmunity, allergies and tumour immunosurveillance. Hence, understanding the molecular interactions between the antigen presenting cell (APC) and the T cells with non-peptidic specificity is of great relevance. Here, we review current knowledge of this type of T cells, their TCR repertoire, the structural aspects of recognized antigens, the mode of antigen recognition, and their function with special emphasis on their role in infectious diseases.

Show MeSH
Related in: MedlinePlus