Nov. 21, 2007 Immune cells known as T cells help us clear invading microbes, such as HIV, from our bodies, but they can also cause autoimmunity when they inappropriately attack our own tissues. T cells are activated when a receptor on their surface (the TCR) recognizes a specific complex of a peptide fragment bound to a protein known as an MHC molecule.
Defining the peptides identified by T cells mediating autoimmunity and immune responses against invading microbes, as well as harnessing this information for the design of therapeutics and vaccines, is an area of intensive investigation.
New insight into these matters is provided in the November issue of the Journal of Clinical Investigation by two studies that report technical advances in the field. The clinical implications of these are discussed in an accompanying commentary by Luc Teyton from The Scripps Research Institute, La Jolla.
Wahlstrom and colleagues from the Karolinska University Hospital, Sweden, developed a strategy to determine the peptide fragments bound by human MHC molecules activating inappropriate immune responses in vivo. Using this approach they identified 78 peptide fragments bound to the MHC molecule HLA-DR on cells isolated from the lungs of patients with sarcoidosis, an inflammatory disease of the lungs mediated largely by CD4+ T cells.
The authors suggest that this approach might be used to identify the peptides recognized by autoreactive T cells that attack the body to cause diseases such as diabetes and rheumatoid arthritis, information that could lead to the development of new treatment strategies.
By contrast, Le Gall and colleagues from Massachusetts General Hospital and Harvard Medical School, Boston, have provided insight into the peptides recognized by CD8+ T cells fighting infection with HIV. The main peptide fragment of the HIV-1 protein Gag that binds the human MHC molecule HLA-A3 is known as the immunodominant epitope.
In vitro assays determined that the amino acid sequence flanking the immunodominant epitope caused the immunodominance as moving these sequences to flank other peptides increased the frequency with which they bound HLA-A3. The authors therefore suggested that these flanking sequences might be used to enhance the effectiveness of HIV vaccines.
First journal article: Identification of HLA-DR -- bound peptides presented by human bronchoalveolar lavage cells in sarcoidosis
Second journal article: Portable flanking sequences modulate CTL epitope processing
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