Proteins in cell are continually being degraded in proteosome machinery and loaded on MHC's. I was wondering if these peptides or self antigens are displayed and if yes how are they recycled if they can't be processed any further saturating the surface.
Of course they are. The machinery that loads peptides on HLA class II cannot distinguish self from non-self. This is the job of the TCR. This is why we need self-tolerance by CD4+ T-cells!
Yes they are.
In the classical pathway, self antigens are loaded into MHC class I; however, recently it is reported that there is a cross presentation in which self antigens are loaded onto MHCII and therefore activate CD4+ cells to elicit autoimmune responses.
Self-peptides are continuously displayed on the surface of cells. The outcome of this depends on the context. Very broadly speaking, in the thymus, if developing T cells recognise these peptides strongly, they will commit suicide (negative selection). If they recognise them with intermediate affinity, they will become regulatory T cells. If they bind to them with low affinity or not at all, they will become conventional T cells and emigrate into the periphery. In the periphery, self-peptides that are displayed in a non-inflammatory context, will elicit tolerance or no respone. If displayed in an inflammatory context AND there are activated autoreactive T cells around, they might (!) elicit autoimmune responses, if some other things also go wrong. Cross-presentation also occurs in the thymus and the periphery under "normal" conditions and is not "per se" related to autoimmunity.
With respect to saturation, peptide-loaded MHC molecules recycle to the endolysosomal compartment, where peptides can be exchanged.
Again, this is only a very, very rough and incomplete overview. If you want to go into detail, there is a recent, extensive review in Ann Rev Imm: http://www.annualreviews.org/doi/full/10.1146/annurev-immunol-032712-095910?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed&
Ubiquitinated self proteins go to proteasomal processing pathway. Cutting may be different in inflammatory or non-inflammatory conditions. Therefore, prevalence of partucular peptides may be different. Peptides are actively transported into EPR by TAP proteins. Capability of peptides to be bound by MHC class I molecules is determined by the presence of allele specific MHC binding motifs. Unbounded peptides can be further returned into cytoplasm for subsequent recycling or transported by Golgi apparatus into environment of the cell. Unlikely they can load MHC class II molecules, because they are too short. To be processed for presentation by MHC class II molecules, proteins should be phagocytosed (or pinocytosed) from external environment of cell and processed in phagolysosomes by catepsins.
Yes, self peptides are presented, but the outcome depends on the T cell repertoire initailly selected in thymus. T cells are in a continous survillance of antigens self and non-self, the response depends on the circumstances
Of course they are. The machinery that loads peptides on HLA class II cannot distinguish self from non-self. This is the job of the TCR. This is why we need self-tolerance by CD4+ T-cells!
MHC molecules can not discriminate between self and foreign peptides. The TCR does.
MHC molecules present self and foreign peptides as well as mutated self peptides.
Dear Abbas,
self peptides are indeed also presented but the T cell repertoire is shaped in the thymus. This is called "negative selection". The result is that only naive T cells with a comparatively low affinity to the presented self antigens are passing the thymus. So-called mTEC cells are responsible for the presentation of the self antigens in the thymus. For details see the work of Kyewski et al.
Best wishes
Christoph Leder
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