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shaped by clusters of polymorphic MHC residues and are thus of distinct chemical and size characteristics in different MHC alleles. For example, a negatively charged side-chain in one MHC molecule may preferentially interact with positively charged peptide residues, while a positively charged side-chain in another MHC molecule may only bind to negatively charged peptide residues; similarly, a small side-chain in one MHC molecule may greatly extend a pocket and allow for interaction with many different amino acid residues, while a large amino acid side-chain in another MHC molecule may completely block access to this pocket. MHC alleles can therefore be characterized by differences in the precise nature and position of polymorphic pockets, thereby playing a major role in allele-specific peptide binding.

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