A hitherto unknown blind spot in immune recognition has been identified by a research team led by Máté Manczinger, a research fellow at the ELKH Biological Research Centre in Szeged (BRC). This phenomenon, which is due to a lack of T cells specific for certain molecules, may also play an important role in the variable efficacy of vaccines and the development of immune responses to tumours. The paper on the subject was published in the prestigious journal of the American Academy of Sciences, PNAS.

For our bodies to function normally, it is essential that our immune systems recognize and destroy pathogens, while tolerating our own cells. T cells, which are specific to a particular set of molecules, play a crucial role in this recognition. When T cells recognize this specific motif, they are able to destroy the pathogen that carries it. In theory, specific T cells can be generated to recognize any motif, but it would be extremely uneconomical for an organism to have T cells for every conceivable motif that does not occur naturally. To avoid this, our immune systems uses motifs in the thymus that occur in our bodies as models during ontogeny. As a result, only those T cells that recognize them survive, while the others die off. Many of these motifs are also found in pathogens, and an effective immune response can be developed against those motifs present in the pathogen when immune function is well regulated. The BRC researchers were looking to learn whether the immune system really benefits from using our own molecules as a model.

It is a generally accepted among immunologists that the more different a foreign molecule is from our own, the more likely it is to elicit an immune response. However, the researchers’ latest findings do not support this: a blind spot in immune recognition is created because T cells use our own molecules as a model during their maturation. Our immune system is unable to recognize molecules that are too different from our own because we do not have T-cells specific to them. Many pathogens contain very high levels of these molecules, so they are more likely to evade our immune systems. The results help to better understand why our immune system reacts to certain molecules and fails to recognize others, even when they are significantly different from our own. This phenomenon may also play an important role in the changing efficacy of vaccines and in the development of the immune response to tumours, which the research team is currently investigating.

The researchers arrived at their findings through a comprehensive analysis of a large number of experimental results, and also supported their hypothesis by directly examining T cells from healthy individuals.

The research involved: Máté Manczinger (researcher at the BRC, head of the research group), Balázs Koncz (PhD student), Lajos Kemény (Director of the Department of Dermatology and Allergology at SZTE-AOK), Gergő Mihály Balogh (PhD student), Benjamin Papp (PhD student), Leó Asztalos (student at the Szeged Academy of Scholars and medical student at SZTE-AOK).

Publication:

Balázs Koncz, Gergő Mihály Balogh, Benjamin Tamás Papp, Leó Asztalos, Lajos Kemény, Máté Manczinger: Self-mediated positive selection of T cells sets an obstacle to the recognition of nonself. PNAS (2021).