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Visualizing Antigen Specific CD4+ T Cells using MHC Class II Tetramers
15:42

Visualizing Antigen Specific CD4+ T Cells using MHC Class II Tetramers

Published on: March 6, 2009

Human cytomegalovirus-specific CD4(+) T-cell clones recognize cross-reactive peptides from the immediate early 1

Emmanuelle Le Roy1, Jean-Luc Davignon

  • 1INSERM U563, Toulouse, CPTP, Institut Claude de Préval, Toulouse Cedex, France.

Viral Immunology
|July 23, 2005
PubMed

Insights

Human cytomegalovirus (HCMV) infection involves T cells recognizing viral proteins. This study shows HLA-DR8 restricted CD4(+) T cells can cross-recognize similar sequences in HCMV IE1 protein, impacting T cell memory.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Human cytomegalovirus (HCMV) establishes lifelong latency in immunocompetent individuals.
  • High frequencies of CD4(+) and CD8(+) T lymphocytes are observed in HCMV-seropositive individuals, crucial for infection control.
  • Mechanisms maintaining these T cell frequencies during latent HCMV infection are not fully understood.

Purpose of the Study:

  • To investigate if sequence homology within the HCMV IE1 protein can lead to cross-recognition by HLA-DR8-restricted CD4(+) T cells.
  • To explore the implications of this cross-recognition for T cell repertoire formation and memory.

Main Methods:

  • Analysis of sequence homology between canonical and previously reported epitopes of the HCMV IE1 protein.
  • Testing established HLA-DR8-restricted T cell clones for cross-recognition of homologous IE1 peptide sequences (IE1 (91-110) and IE1 (91-104)).
  • Generation and characterization of new IE1-specific, HLA-DR8-restricted CD4(+) T cell clones from seropositive donors using the homologous peptide.

Main Results:

  • Established HLA-DR8-restricted T cell clones demonstrated cross-recognition of the IE1 (91-110) peptide and a shorter variant, IE1 (91-104).
  • The homologous peptide IE1 (91-110) successfully generated new, cross-reactive IE1-specific, HLA-DR8-restricted CD4(+) T cell clones from HCMV-seropositive individuals.
  • These findings suggest a mechanism for T cell repertoire expansion and maintenance during chronic viral infections.

Conclusions:

  • Sequence homology within viral proteins, such as HCMV IE1, can drive cross-recognition by T cells.
  • This cross-recognition phenomenon may contribute to the generation and regulation of the T cell repertoire and memory during persistent infections.
  • Understanding these mechanisms offers insights into immune responses against latent viruses like HCMV.

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