The effect of anchor residue modifications on the stability of major histocompatibility complex class I-peptide interactions.
Anchor residues in peptides determine the specificity of binding to major histocompatibility complex class I molecules through interactions of their side chains with pockets in the peptide-binding groove. We have compared the kinetics of association of a Sendai virus nucleoprotein-derived peptide (FAPGNYPAL, termed SV9) with H-2Kb class I molecules, and the same peptide iodinated on the anchor residue tyrosine (125I-SV9). Even though the association rates were too rapid for direct measurements, competition studies indicated that they were similar for SV9 and 125I-SV9. To measure the binding of non-radioactive SV9 directly, SV9 was tritiated (3H-SV9). 3H-SV9 remained stably associated with H-2Kb molecules, whereas 125I-SV9 dissociated in a temperature-dependent fashion. Thus, modifications on anchor residues do not necessarily have to affect the specificity and association kinetics of peptide binding to class I molecules but can affect the stability of the resulting class I-peptide interaction. The dissociation of peptides with modified and, more generally, suboptimal anchor residue side chains may explain the presence of empty class I molecules and free class I heavy chains at the cell surface.
The Netherlands Cancer Institute, Dept. Cellular Biochemistry, Amsterdam.
J J
JJ
Neefjes
J
J
Dierx
H L
HL
Ploegh
D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000737:chemistry*; D006183:H-2 Antigens / Q000378:metabolism*; D008969:Molecular Sequence Data; D007470:Monoiodotyrosine / Q000737:chemistry; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010222:Parainfluenza Virus 1, Human / Q000276:immunology; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013696:Temperature; D014443:Tyrosine / Q000737:chemistry; D014758:Viral Core Proteins / Q000737:chemistry / Q000276:immunology*
D000956:Antigens, Viral; D006183:H-2 Antigens; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010455:Peptides; D014758:Viral Core Proteins; D014443:Tyrosine; D007470:Monoiodotyrosine