A NATURALLY PROCESSED PEPTIDE PRESENTED BY HLA-A-ASTERISK-0201 IS EXPRESSED AT LOW ABUNDANCE AND RECOGNIZED BY AN ALLOREACTIVE CD8(-CELL WITH APPARENT HIGH-AFFINITY() CYTOTOXIC T)
W. Wang et al., A NATURALLY PROCESSED PEPTIDE PRESENTED BY HLA-A-ASTERISK-0201 IS EXPRESSED AT LOW ABUNDANCE AND RECOGNIZED BY AN ALLOREACTIVE CD8(-CELL WITH APPARENT HIGH-AFFINITY() CYTOTOXIC T), The Journal of immunology, 158(12), 1997, pp. 5797-5804
In contrast to T cells that respond to peptides presented by self MHC
molecules, alloreactive T cells recognize determinants expressed on no
nself MHC molecules. Because current positive selection models suggest
that T cell affinity toward a nonself MHC molecule would be lower tha
n that toward a self MHC molecule, we previously proposed that vigorou
s alloreactive responses would be generated preferentially toward thos
e antigenic peptide complexes presented at the highest density on the
cell surface. The high abundance of two class I MHC-associated peptide
s that have been identified as allo- or xenoantigens is consistent wit
h this hypothesis, We report here the identification of a naturally pr
ocessed peptide YLDPAQQNL that is presented by HLA-A0201 and recogniz
ed by an alloreactive T cell clone. This peptide appears to originate
from an unknown member of the zinc finger proteins. Quantitation by ma
ss spectrometry indicates that this peptide is present on the surface
at 85 to 125 copies per cell, comparable with the density of several o
ther epitopes presented by HLA-A0201 to self MHC-restricted T cells.
In addition, based on the affinity of the peptide for HLA-A0201 and t
he half-maximal peptide concentration required for T cell sensitizatio
n, this alloreactive T cell appears to have an affinity similar to or
higher than that of many self MHC-restricted T cells. These data sugge
st that allogeneic responses can be directed against antigenic determi
nants of low abundance and that recognition of alloreactive peptides i
s not limited by a lower affinity of T cells for nonself MHC molecules
.