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The T-cell receptor as immunoglobulin: paradigm regained
J J Marchalonis1, S F Schluter, A B Edmundson
1Department of Microbiology and Immunology, College of Medicine, University of Arizona, Tucson 85724-5049, USA.
Summary
T-cell receptors (TCRs) are members of the immunoglobulin superfamily, sharing structural and functional similarities with conventional antibodies. This evolutionary link aids understanding of both TCRs and immunoglobulins, revealing conserved mechanisms in antigen recognition.
Area of Science:
- Immunology
- Molecular Biology
- Structural Biology
Background:
- The molecular identity of T-lymphocyte receptors for antigens remained elusive for over 25 years.
- Previous hypotheses suggested T-cell receptors (TCRs) lacked major histocompatibility complex determinants but possessed Ig-related regions.
Observation:
- Subsequent research in molecular biology, protein chemistry, and structural biology confirmed TCRs as members of the immunoglobulin superfamily.
- TCRs share structural features, sequence homology, and diversification mechanisms with conventional immunoglobulins.
- These molecules emerged in vertebrate evolution alongside sharks.
Findings:
- TCRs and immunoglobulins (Igs) exhibit conserved evolutionary origins and structural similarities.
- Concepts from Ig research illuminate TCR function, while TCR insights, like superantigens, apply to Igs.
- X-ray crystallography reveals TCRs recognize both MHC and peptide epitopes, akin to antibodies.
Implications:
- Understanding the Ig-TCR relationship deepens insights into adaptive immunity and antigen recognition.
- The existence of MHC-restricted antibodies is supported by TCR structural data.
- Further research is expected to identify more antigen-specific immunoglobulin family members in mammals.