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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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Related in: MedlinePlus

Structure of isopenenylpyrophosphate, IPP (A) and (E)-4-hydroxy-3-methyl-but-2- enyl pyrophosphate (HMBPP) (B).
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Figure 1: Structure of isopenenylpyrophosphate, IPP (A) and (E)-4-hydroxy-3-methyl-but-2- enyl pyrophosphate (HMBPP) (B).

Mentions: The major population of human γδ T cells that expresses the TCR Vγ9Vδ2 recognizes small phosphorylated metabolites. These molecules are isopentenylpyrophosphate (IPP) generated in the mevalonate pathway6263, and 4-hydoxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) that is an intermediate metabolite of the 2-C-methyl-D-erythritol 4-phosphate biosynthetic pathway present in several microorganisms64 (Fig. 1). These antigens closely resemble each other, although HMBPP shows 1000 times higher potency than IPP when added exogenously to APCs. The fact that the microbial metabolite is very potent supports the hypothesis that this major T cell population is involved in anti-microbial surveillance. Comparison of the potency of different synthetic analogs of IPP has shown that the length and structure of the alkyl chain are important for immunogenicity. Indeed, methylphosphate is active, whereas dimethylphosphate and trimethylphosphate are not stimulatory65. Also, the number and position of the phosphate groups play a critical role66. An important finding was that drugs capable of inhibiting the mevalonate pathway also controlled the activation of γδ T cells. Aminobisphosphonates stimulate Vγ9Vδ2 cells by inhibiting the late steps of the mevalonate pathway, and inducing the accumulation of IPP, an intermediate metabolite67. The mechanism how these antigens interact with TCR γδ remains unclear. Studies have indicated that APCs are important, and that IPP and HMBPP require presentation by dedicated antigen-presenting molecules, which are non-polymorphic, ubiquitous and species-specific68697071.


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

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

Structure of isopenenylpyrophosphate, IPP (A) and (E)-4-hydroxy-3-methyl-but-2- enyl pyrophosphate (HMBPP) (B).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Structure of isopenenylpyrophosphate, IPP (A) and (E)-4-hydroxy-3-methyl-but-2- enyl pyrophosphate (HMBPP) (B).
Mentions: The major population of human γδ T cells that expresses the TCR Vγ9Vδ2 recognizes small phosphorylated metabolites. These molecules are isopentenylpyrophosphate (IPP) generated in the mevalonate pathway6263, and 4-hydoxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) that is an intermediate metabolite of the 2-C-methyl-D-erythritol 4-phosphate biosynthetic pathway present in several microorganisms64 (Fig. 1). These antigens closely resemble each other, although HMBPP shows 1000 times higher potency than IPP when added exogenously to APCs. The fact that the microbial metabolite is very potent supports the hypothesis that this major T cell population is involved in anti-microbial surveillance. Comparison of the potency of different synthetic analogs of IPP has shown that the length and structure of the alkyl chain are important for immunogenicity. Indeed, methylphosphate is active, whereas dimethylphosphate and trimethylphosphate are not stimulatory65. Also, the number and position of the phosphate groups play a critical role66. An important finding was that drugs capable of inhibiting the mevalonate pathway also controlled the activation of γδ T cells. Aminobisphosphonates stimulate Vγ9Vδ2 cells by inhibiting the late steps of the mevalonate pathway, and inducing the accumulation of IPP, an intermediate metabolite67. The mechanism how these antigens interact with TCR γδ remains unclear. Studies have indicated that APCs are important, and that IPP and HMBPP require presentation by dedicated antigen-presenting molecules, which are non-polymorphic, ubiquitous and species-specific68697071.

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