THEME 6 IMAGING LIPID-MEDIATED IMMUNITY

Allergens and cosmetics. Artwork of a moisturiser jar containing a depiction of the immune molecule, CD1a, binding to the allergic compound
Dr Erica Tandori, artist in residence from the Rossjohn Laboratory at Monash University.

“We know how some of the compounds found in skin care products and cosmetics can directly interact with human
proteins in the skin known as CD1a.”

As well as T cells sensing peptides presented by MHC molecules (Theme 5), they can also respond to lipids (this theme) and metabolites (Theme 7). In the context of lipid-mediated immunity, TCRs recognise lipids that are presented by MHC-I like molecules, namely the CD1 family.

There are four members of the CD1 family of antigen-presenting molecules expressed on the cell surface (CD1a,b,c,d), each one of which possesses unique structural and biochemical/cellular features that indicates distinct roles in immunity. Indeed, it is now becoming evident – in part due to the contributions of Imaging CoE scientists, that the CD1 family can play an important role in both protective immunity (e.g. response to Mycobacterium tuberculosis) and immunopathology. Imaging CoE scientists continue to pioneer this aspect of immunity.

PROF. JAMIE ROSSJOHN
PROF. DALE GODFREY

AT A GLANCE

Findings in this area has led to an understanding of:
  1. How lipid-based allergens can mediate contact hypersensitivity (Nicolai et al., Science Immunol)
  2. A mechanism of CD1b-mediated T cell autoreactivity (Shahine et al., Nature Comms)
  3. TCR bias in the immune response to CD1 molecules (Reinink et al., JI)
  4. Distinct docking strategies of type II NKT TCRs upon CD1d (Almeida et al., Nature Comms)

ACTIVITY PLAN

 

  1. Explore the range of lipid antigens presented by CD1 and the ensuing immune response.

HIGHLIGHT

Discovery shines light on the cause of some allergic responses

A team of international researchers from Monash University, Columbia University and Harvard Medical School has discovered how some compounds contained in cosmetic and perfume products can activate human T cells, the sentinels of our immune system.

It’s long been known that certain chemicals cause allergic contact dermatitis (ACD), but our understanding of why this is happening is still very limited.

The teams led by Monash University’s Prof. Jamie Rossjohn, Dr Annemieke de Jong from Columbia University and Harvard Medical School’s Dr Branch Moody investigated the role a common protein in the skin – known as CD1a – could play in allergic reactions to cosmetics.

Researchers found more than a dozen small compounds that were able to associate with the CD1a protein leading to an immune response in human T cell culture.

“Normally, many CD1a molecules are filled with natural blockers in our bodies that would prevent an exaggerated immune response, and those small compounds basically remove those natural blockers” says Dr Marcin Wegrecki, who together with Dr Jerome Le Nours, was part of the Monash University team involved in the study.

Part of the research focused on small chemicals found in many essential oils and botanical extracts such as the Balsam of Peru, an oily tree resin found in many cosmetic products, toothpastes and fragrances.

“Balsam of Peru was also used in natural products because it comes from a tree – it’s not chemically synthesised – so it was very popular. But unfortunately a significant number of people – up to five per cent of the population – is allergic to it because it contains all those small compounds,” he said.

Using a high energy X-ray beam at the Australian Synchrotron at Monash University, the researchers were able to describe the way CD1a and farnesol, another common additive in cosmetics and skin creams, interact at a molecular level.

Dr Wegrecki, a Monash BDI researcher said the results published in Science Immunology, gave more clarity around what was happening. “Now we know how some of the compounds found in skin care products and cosmetics can directly interact with human proteins,” he said.

Despite the known allergy, Balsam of Peru is still used in some products, including toothpaste, sunscreen, face creams and cosmetics.

Further research into the clinical significance of these molecular findings could now help scientists understand how those small chemicals induce ACD and potentially design strategies to revert their allergenic effect.

Article Source:
Monash University 

Allergens and cosmetics. Artwork of a moisturiser jar containing a depiction of the immune molecule, CD1a, binding to the allergic compound.

Credit: Dr Erica Tandori, artist in residence, Rossjohn Laboratory at Monash University.

ACHIEVEMENT

EMBO Workshop CD1-MR1: Beyond MHC-restricted lymphocytes – Oxford, UK

A number of Imaging CoE researchers from Prof. Jamie Rossjohn and Prof. Dale Godfrey’s laboratory attended and presented their research at the international EMBO Workshop at Oxford University in September. The EMBO Workshop, CD1-MR1: Beyond MHC-restricted lymphocytes brought together cross-disciplinary researchers with an expertise in T cells which recognise antigens presented by the MHC-like molecules CD1 and MR1. These bi-annual forums encourage cross-disciplinary networking and help to establish new international collaborations. The workshops are connected to a number of high-impact publications.

“It is a major conference which covers lipid and metabolite mediated immunity. The conference is a great opportunity to showcase the Imaging CoE’s research and learn new techniques from scientists around the world, “ said Prof. Jamie Rossjohn.

Imaging CoE researchers, Adam Shahine, Marcin Wegrecki, Lauren Howson, Catarina Dos Santos Sa E Almeida, Jerome Le Nours and Wael Awad all presented their research to an international audience.

“It’s a great and prestigious experience for our early career researchers to present their work in such a constructive and supportive environment,” Prof. Rossjohn said.

Lauren Howson (top) and Marcin Wegrecki (bottom) share the latest MAIT cell research from the Rossjohn Lab