From left to right: Mark Brockman, PhD student and co-author Gursev Anmole and research assistant Rachel Miller examining T-cells in the lab.

Researchers from the University of KwaZulu-Natal (UKZN) and
the Simon Fraser University (SFU) in Canada have identified a connection
between infection control and how well antiviral T cells respond to diverse HIV
sequences.  which may help efforts to
produce an HIV vaccine.

SFU professor Mark Brockman and co-authors from the
University of KwaZulu-Natal hope that their research will help efforts to
produce an HIV vaccine.

Brockman explains that HIV adapts to the human immune system
by altering its sequence to evade helpful antiviral T cells. “Development of an
effective HIV vaccine will therefore require the generation of host immune
responses that the virus cannot evade easily,” he says.

Brockman’s team developed new laboratory-based methods to
identify antiviral T cells and to assess their ability to recognise diverse HIV

“T cells are white blood cells that are able to recognise
foreign particles called peptide antigens,” says Brockman. “There are two
major types of these cells, those that ‘help’ other cells of the immune system
and those that kill infected cells and tumours.”

It sounds like a simple solution to identify those T cells
that attack HIV antigens, but Brockman says three biological factors are
critical to a T cell-mediated immune response — and all three are highly
genetically diverse in the case of HIV infection.

For a T cell to recognise a peptide antigen, it must first
be presented on the cell surface by human leukocyte antigen proteins (HLA). HLA
genes are inherited and many thousands of possible variants exist in the human
population, so every person’s response to infection is unique. In addition, HIV
is highly diverse and evolves constantly during untreated infection, so the
peptide antigen sequence can change.

Matching T cells against the HLA variants and HIV peptide
antigens expressed in an individual is a critical step in the process that is
routinely done for research, but Brockman says, “our understanding of T cell
responses will be incomplete until we know more about the antiviral activity of
individual T cells that contribute to this response.”

It is estimated that a person’s T cell “repertoire” is made
up of a possible 20-100 million unique lineages of cells that can be
distinguished by their T cell receptors (TCR), of which only a few will be
important in responding to a specific antigen.

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

By looking at how well individual T cells recognised TL9 and
diverse TL9 sequence variants that occur in circulating HIV strains, they found
that T cells from people who expressed HLA B81 recognised more TL9 variants
compared to T cells from people who expressed HLA B42.

Notably, a group of T cells in some B42-expressing
individuals displayed a greater ability to recognise TL9 sequence variants, and
the presence of these T cells was associated with better control of HIV

This study demonstrates that individual T cells differ
widely 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 work needs to be done to create an effective vaccine.
However, says Brockman, “comprehensive methods to assess the ability of T cells
to recognise diverse HIV sequences, such as those reported in this study,
provide critical information to help design and test new vaccine strategies.”


Reference: Brockman
MA, et al.Dual HLA B*42 and B*81-reactive T cell receptors recognize more
diverse HIV-1 Gag escape variants. Nature Communications.