Conserved TcR beta chain usage for a single MHC class II-restricted heat shock protein peptide

Area of Science:

• Immunology
• T-cell biology
• Molecular genetics

Background:

• T-cell responses are crucial in infectious diseases like leprosy.
• Previous work identified a restricted T-cell receptor (TcR) usage in a tuberculoid leprosy patient against a specific heat shock protein (hsp65 aa 3-13) peptide.
• The role of TcR repertoire diversity in healthy individuals responding to the same antigen was unclear.

Purpose of the Study:

• To analyze the T-cell receptor (TcR) repertoire in healthy individuals responding to the heat shock protein (hsp65 aa 3-13) peptide.
• To compare the TcR diversity in healthy high responders with that of a tuberculoid leprosy patient.
• To investigate the implications of TcR usage and diversity in disease versus healthy states.

Main Methods:

• Analysis of T-cell receptor (TcR) sequences from T-cell clones specific for the hsp65 aa 3-13 peptide.
• Comparison of TcR V-beta (TRBV) gene usage and CDR3 region sequences.
• Characterization of T-cell responses in three healthy individuals and one tuberculoid leprosy patient.

Main Results:

• Healthy high responders exhibited a diverse T-cell response to the hsp65 aa 3-13 peptide, unlike the leprosy patient.
• Despite diversity, TRBV5-expressing T-cell clones nearly identical to the dominant clone in the leprosy patient were found in two healthy individuals.
• TcR restriction specific for an antigen correlates with its presence in disease, but preferred TcRs can also exist in healthy individuals.

Conclusions:

• Antigen presence during disease may lead to T-cell receptor (TcR) repertoire restriction.
• The T-cell receptor (TcR) repertoire in healthy individuals can be diverse, yet may contain specific clones also dominant in disease states.
• In vivo natural infection, as in leprosy, might drive the selection and expansion of specific TcRs.