Researchers find new clues to control HIV

The immune system is the best defense of the body in the fight against diseases such as HIV and cancer. Now, an international team of researchers is using the immune system to reveal new clues that can contribute to HIV vaccine production efforts.

Professor Mark Brockman of SFU and co-authors of the University of KwaZulu-Natal, South Africa, have identified a link between infection control and the degree of antiviral T cell response to various sequences of HIV.

Brockman explains that HIV adapts to the human immune system by modifying its sequence to avoid useful antiviral T cells.

"So, to develop an effective HIV vaccine, we need to generate host immune responses that the virus can not easily escape," he said.

The Brockman team has developed new laboratory methods for identifying antiviral T cells and badessing their ability to recognize various HIV sequences.

"T cells are white blood cells that can recognize foreign particles called peptide antigens," says Brockman. "There are two main types of T cells: those that" help "other cells in the immune system and those that destroy infected cells and tumors."

Identifying the T cells that attack the HIV antigens seems simple, but Brockman says that three biological factors are essential for a T-cell mediated immune response. And in HIV infection, the three species are very diverse in the immune system. genetic plan.

He explains that for a T cell to recognize a peptide antigen, the antigen must first be presented on the cell surface by human leukocyte antigen (HLA) proteins. , which are inherited.

And since there are many thousands of HLA variants in the human population, each person responds differently to the infection. In addition, since HIV is very diverse and constantly evolving during an untreated infection, the sequence of the peptide antigen also changes.

The correspondence of T cells with HLA variants and HIV peptide antigens expressed in an individual is a crucial step in the routine search process. But, says Brockman, "our understanding of T cell responses will be incomplete until we know more about the antiviral activity of the individual T cells that contribute to this response."

It is estimated that the "repertoire" of a person's T cells consists of 20 to 100 million unique cell lines that can be distinguished by their T cell receptors (TCRs), of which only a few will be important for respond to a specific antigen.

To reduce the complexity of the study, the team therefore examined two highly related HLA variants (B81 and B42) recognizing the same HIV peptide antigen (TL9), but badociated with different clinical outcomes following infection. .

In examining the extent to which individual T cells recognize TL9 and various TL9 sequence variants in circulating HIV strains, the researchers found that the T cells of HLA B81-expressing individuals recognized more variants of TL9 than the T cells of people expressing HLA B42.

Notably, a group of T cells in some individuals expressing B42 has shown greater ability to recognize TL9 sequence variants. The presence of these T cells was badociated with better control of HIV infection.

This study demonstrates that individual T cells are very different in their ability to recognize peptide variants and suggests that these differences may be clinically significant in the context of a diverse or rapidly evolving pathogen such as HIV.

Much remains to be done to create an effective vaccine. However, says Brockman, "Comprehensive methods to evaluate the ability of T cells to recognize various HIV sequences, such as those reported in this study, provide essential information to help design and test new vaccine strategies."

Provided by
Simon Fraser University