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Novel Immunomodulatory Pathways in the Immunoglobulin Superfamily

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Novel Immunotherapeutic Approaches to the Treatment of Cancer

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Abstract

The immunoglobulin superfamily (IgSF) is a large and highly diverse assemblage of related proteins that regulate many different biological processes. The name of the family is based on early studies demonstrating sequence similarity between the antibody (immunoglobulin) variable and constant domains, showing an ancestral link, and the subsequent identification of proteins with similar sequences, suggesting broad diversification and evolution (Williams and Barclay, Annu Rev Immunol 6: 381–405, 1988). Antibodies, the T cell receptors (TCR), and the major histocompatibility complex (MHC), among others, are made up of multiple Ig domain chains that assemble to form the final protein, facilitating antigen presentation/recognition (Fig. 2.1a). The individual Ig domains within this family contain a conserved intra-chain disulfide bond that serves to stabilize the domain. These individual structural domains consist of two “sheets” that consist of beta-strands, as illustrated for a generic Ig-domain (Fig. 2.1b). Many IgSF proteins consist of single chains that string together one or more Ig-domains, each with its own intrinsic features. IgSF proteins can have from one to many such domains, and these are characterized as variable (V) domains, as in Fig. 2.1b, or constant (C) domains based on sequence and structural similarity to the domains characterized in antibodies (Fig. 2.1a). Beyond the conserved core motifs, the family has diverged drastically, and many unique and unusual structural features have evolved.

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Abbreviations

APC:

Antigen presenting cells

CEACAM1:

Carcinoembryonic antigen-related cell adhesion molecule 1

DC:

Dendritic cells

ICOS:

Inducible T-cell costimulator

IgSF:

Immunoglobulin superfamily

ITIM:

Immunoreceptor tyrosine-based inhibition motif

LAG-3:

Lymphocyte activation gene-3

MDSC:

Myeloid-derived suppressor cells

MHC:

Major histocompatibility complex

PS:

Phosphatidylserine

PVR:

Poliovirus receptor

TCR:

T cell receptor

TIGIT:

T cell immunoglobulin and ITIM domain

TIL:

Tumor-infiltrating lymphocytes

TIM:

T cell immunoglobulin mucin

VISTA:

V-domain immunoglobulin (Ig)-containing suppressor of T-cell activation

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    Paul D. Rennert

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    Paul D. Rennert

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Rennert, P.D. (2016). Novel Immunomodulatory Pathways in the Immunoglobulin Superfamily. In: Rennert, P. (eds) Novel Immunotherapeutic Approaches to the Treatment of Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-29827-6_2

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